Affinage

BOC

Brother of CDO · UniProt Q9BWV1

Length
1114 aa
Mass
121.1 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BOC is a transmembrane co-receptor of the Ig/fibronectin superfamily that binds all three mammalian Hedgehog ligands through a specific fibronectin repeat domain and, together with the functionally overlapping co-receptors CDON and GAS1, forms obligatory complexes with Patched1 to transduce Hedgehog signaling in multiple developmental contexts (PMID:16647304, PMID:21664577, PMID:20519495). These co-receptor complexes are collectively essential for Hedgehog-dependent ventral neural patterning, cerebellar granule neuron progenitor proliferation, craniofacial morphogenesis, myelination, adipogenesis suppression, and primordial germ cell migration, with BOC exerting tissue-specific promoting or restraining effects on pathway output (PMID:21664576, PMID:33060130, PMID:31048318, PMID:25576054, PMID:32332736). In axon guidance, BOC functions as a direct Shh receptor on commissural and retinal ganglion cell neurons: Shh binding triggers Numb-dependent BOC internalization into early endosomes, which gates Ptch1 endocytosis and couples ligand reception to growth-cone turning and axon trajectory decisions at the optic chiasm (PMID:17086203, PMID:20053908, PMID:31054872). Missense BOC variants with altered Shh signaling activity have been identified in holoprosencephaly patients, and compound Boc;Cdon loss in mice produces holoprosencephaly-spectrum defects, establishing BOC as a modifier of this disorder (PMID:28677295, PMID:11782431).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    BOC was identified as a partner of CDO that promotes myogenic differentiation, establishing it as a cell-surface molecule with signaling function in cell fate determination—though its ligand was unknown.

    Evidence Co-immunoprecipitation of BOC–CDO, soluble ectodomain fusion protein and dominant-negative CDO epistasis in myoblast differentiation assays

    PMID:11782431

    Open questions at the time
    • No ligand identified for BOC
    • Mechanism of CDO-dependent signaling unknown
    • Intracellular signaling pathways downstream of BOC uncharacterized
  2. 2005 Medium

    Zebrafish boc knockdown revealed that BOC functions in axon guidance of ventrally projecting tracts, providing the first evidence it acts in neural circuit wiring rather than solely in myogenesis.

    Evidence Antisense morpholino knockdown in zebrafish with axon tract immunostaining

    PMID:15776441

    Open questions at the time
    • Morpholino-only approach lacks genetic confirmation
    • No ligand identified for axon guidance function
    • Mammalian relevance not yet shown
  3. 2006 High

    Two landmark studies established that BOC directly binds Sonic Hedgehog through a fibronectin repeat domain and functions both as a Shh-dependent ventral neural patterning co-receptor and as the receptor mediating Shh-guided commissural axon pathfinding—unifying its ligand identity and its roles in patterning and guidance.

    Evidence Domain-mapping binding assays, ectopic expression in neural tube, Boc knockout mice with commissural axon tracing, in vitro growth-cone turning assay with Boc RNAi

    PMID:16647304 PMID:17086203

    Open questions at the time
    • How BOC transduces signal intracellularly unresolved
    • Relationship between BOC and Ptch1 in receptor complex unknown
    • Redundancy with CDON and GAS1 not yet genetically dissected
  4. 2010 High

    Crystal structures of Hedgehog–BOC complexes and functional studies in retinal ganglion cells defined the structural basis of BOC–Hh binding and extended BOC's axon-guidance role to ipsilateral RGC segregation at the optic chiasm, while genetic epistasis with Cdon revealed BOC as a holoprosencephaly modifier.

    Evidence X-ray crystallography of Hh–BOC/CDO complexes, in vitro RGC axon retraction and in vivo gain/loss-of-function at the optic chiasm, Cdo;Boc double-knockout mouse analysis

    PMID:20053908 PMID:20519495 PMID:21183473

    Open questions at the time
    • No structural information on full receptor complex (BOC–Ptch1–Shh)
    • Mechanism of intracellular signal transduction from BOC still unknown
    • Functional distinction between BOC and CDON at molecular level not resolved
  5. 2011 High

    Compound genetic knockouts demonstrated that BOC, CDON, and GAS1 are collectively obligatory for all Hedgehog pathway activity and form distinct complexes with Ptch1—resolving the longstanding question of whether co-receptors are merely modulatory or essential.

    Evidence Single/double/triple mutant mice with neural patterning readouts; co-immunoprecipitation of BOC–Ptch1 complex; mutant Hh ligand that binds Ptch1 but not co-receptors fails to signal

    PMID:21664576 PMID:21664577

    Open questions at the time
    • Molecular mechanism by which co-receptor binding enables Smo de-repression unknown
    • Tissue-specific deployment of individual co-receptors not fully understood
    • Structural basis of BOC–Ptch1 interaction unresolved
  6. 2013 Medium

    Boc was shown to be required for sustained generation of ipsilateral RGCs through regulation of Zic2 expression, demonstrating that BOC-mediated Shh signaling controls retinal cell fate specification beyond axon guidance.

    Evidence Boc knockout mouse retinal analysis with Zic2/Islet2 immunostaining and in vivo electroporation

    PMID:23678105

    Open questions at the time
    • Direct versus indirect regulation of Zic2 by Shh/Boc not resolved
    • Whether BOC acts cell-autonomously in iRGC fate specification not fully established
  7. 2014 High

    BOC was found to promote medulloblastoma by amplifying Shh signaling to levels that drive CyclinD1-mediated DNA damage and Ptch1 loss-of-heterozygosity, providing a mechanistic link between co-receptor dosage and tumor progression.

    Evidence Boc knockout in Ptch1+/− medulloblastoma model, CyclinD1 manipulation, LOH analysis

    PMID:25263791

    Open questions at the time
    • Whether BOC also contributes to other Hh-driven cancers untested
    • Relative contributions of BOC versus CDON/GAS1 to medulloblastoma not dissected
  8. 2015 Medium

    Structure-function analysis revealed that CDON and BOC utilize distinct extracellular motifs and membrane-attachment requirements to promote Hh signaling, while Boc knockout mice showed age-related adiposity linked to reduced Hh pathway activity—extending BOC's physiological roles to metabolic regulation.

    Evidence Chick spinal cord electroporation with domain deletion/swap mutants; Boc knockout mouse adiposity and MEF adipogenesis assays

    PMID:25576054 PMID:25848697

    Open questions at the time
    • Structural determinants of BOC-specific signaling versus CDON not fully mapped
    • Mechanism by which Hh pathway suppresses adipogenesis downstream of BOC not characterized
  9. 2016 Medium

    BOC was shown to interact with ABL kinase through an SH2-binding motif and to require ABL-dependent JNK activation for neuronal differentiation, identifying an intracellular signaling pathway linking BOC to non-canonical Hh outputs.

    Evidence Co-immunoprecipitation of BOC–ABL, ABL-binding-defective BOC mutants, JNK activation assay, neurite outgrowth in Boc−/− neural progenitors

    PMID:27871935

    Open questions at the time
    • ABL–BOC interaction not validated by orthogonal methods
    • Relationship between ABL/JNK pathway and canonical Hh/Smo signaling unclear
    • In vivo relevance of BOC–ABL axis not tested
  10. 2017 Medium

    Identification of BOC missense variants in holoprosencephaly patients with altered signaling properties confirmed BOC as a human disease modifier gene, bridging mouse genetics to clinical relevance.

    Evidence Cell-based SHH signaling assays with patient-derived BOC variants

    PMID:28677295

    Open questions at the time
    • No family cosegregation or in vivo rescue for individual variants
    • Functional consequences of variants on co-receptor complex formation untested
  11. 2019 High

    The mechanistic basis of BOC in axon guidance was resolved: Shh triggers Numb-dependent BOC internalization into early endosomes, which is required for Ptch1 endocytosis and downstream signaling in growth-cone turning—establishing BOC as an endocytic platform rather than a passive ligand-binding partner.

    Evidence Endosome fractionation, live imaging of BOC internalization, Co-IP of BOC–Numb, Numb RNAi, in vitro turning assay, in vivo commissural axon tracing

    PMID:31054872

    Open questions at the time
    • Whether Numb-dependent internalization operates in non-neuronal Hh signaling contexts unknown
    • Endosomal signaling events downstream of BOC/Ptch1 internalization uncharacterized
  12. 2019 Medium

    Boc was found to be required for normal myelination timing and oligodendrocyte precursor differentiation, extending its roles to glial biology.

    Evidence Boc knockout mouse analysis with oligodendroglial markers, MBP quantification, myelin repair assay

    PMID:31048318

    Open questions at the time
    • Cell-autonomous versus non-cell-autonomous role of Boc in OPCs not resolved
    • Whether Hh signaling mediates all myelination effects of Boc unclear
  13. 2020 Medium

    Distinct Ptch1/Boc and Ptch2/Gas1 hetero-complexes were identified with different signaling kinetics, and BOC was shown to have tissue-specific restraining roles on Hh signaling during craniofacial development—resolving the paradox of opposing BOC phenotypes across tissues.

    Evidence Co-IP of Ptch1/Boc versus Ptch2/Gas1 complexes, compound mouse knockouts, PGC migration assays, craniofacial morphometry with Hh target gene analysis

    PMID:32332736 PMID:33060130

    Open questions at the time
    • Molecular basis of tissue-specific promoting versus restraining functions not resolved
    • Structural basis for selective Ptch1/Boc versus Ptch2/Gas1 complex formation unknown
  14. 2021 Medium

    A DISP–BOC complex was identified in Shh-producing cells that promotes cytoneme formation and ligand delivery, revealing a previously unrecognized role for BOC in signal-sending rather than signal-receiving cells.

    Evidence Co-IP of DISP–BOC, live-cell imaging of cytonemes, Myo10 knockout mouse neural tube analysis

    PMID:33570491

    Open questions at the time
    • Whether BOC functions equivalently in all Hh-producing cell types unknown
    • Mechanism by which DISP–BOC promotes cytoneme formation unresolved
    • Independence from BOC's role in receiving cells not fully tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of full BOC–Ptch1–Shh receptor complexes, the molecular determinants of tissue-specific promoting versus restraining roles, the relationship between canonical (Smo-dependent) and non-canonical (ABL/JNK) signaling downstream of BOC, and whether the DISP–BOC axis in signal-sending cells is separable from co-receptor function in receiving cells.
  • No full-length BOC–Ptch1 structural model
  • Tissue-specific regulatory logic not decoded
  • Non-canonical vs canonical signaling integration unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 2 GO:0005768 endosome 1
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5
Partners
ABL1CDONDISP1GAS1NUMBPTCH1SHH
Complex memberships
CDON-BOC complexDISP-BOC complexPtch1/Boc co-receptor complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 BOC forms cis complexes with CDO via both their ectodomains and intracellular domains, and positively regulates myogenic differentiation; a soluble BOC ectodomain fusion protein promotes myogenesis, indicating the intracellular region is dispensable, but a dominant-negative CDO blocks BOC's pro-myogenic effects, placing BOC dependent on CDO for myogenic activity. Co-immunoprecipitation, soluble fusion protein rescue assay, dominant-negative CDO overexpression, myoblast differentiation assay The EMBO journal High 11782431
2006 BOC and CDO bind Sonic Hedgehog (Shh) through a high-affinity interaction with a specific fibronectin repeat, and ectopic expression of BOC promotes Shh-dependent, cell-autonomous ventral cell fates while producing non-cell-autonomous ventral expansion consistent with Shh sequestration; BOC is a target and component of the Hedgehog signaling feedback network. Binding assays (fibronectin repeat mutants), ectopic expression in neural tube, genetic loss-of-function in mice Developmental cell High 16647304
2006 BOC functions as a receptor for Shh in commissural axon guidance: Boc is expressed by commissural neurons, targeted disruption in mice causes commissural axon misguidance toward the floor plate, and RNAi knockdown of Boc impairs the ability of commissural axons to turn toward an ectopic Shh source in vitro. In vitro growth-cone turning assay, RNAi knockdown, mouse genetic knockout with axon tracing Nature High 17086203
2010 BOC (Shh receptor) is enriched in ipsilateral retinal ganglion cells (RGCs); Boc-positive RGC axons retract in vitro in response to Shh and this retraction is lost in Boc mutant RGCs; in vivo, Boc is required for normal segregation of ipsilateral axons at the optic chiasm, and ectopic Boc expression in contralateral RGCs prevents their axons from crossing the chiasm. In vitro axon retraction assay, Boc mutant mouse analysis, in vivo electroporation of Boc into contralateral RGCs The Journal of neuroscience High 20053908
2010 X-ray crystal structures of Sonic, Indian, and Desert Hedgehog proteins complexed with active domains of CDO and BOC reveal that all mammalian Hh proteins bind CDO and BOC in the same manner, and that Hh–CDO interactions are weakened at low pH; CDO and BOC use non-orthologous domains compared with Drosophila Ihog. X-ray crystallography, biochemical binding assays The Journal of biological chemistry High 20519495
2011 GAS1, CDO, and BOC play overlapping and collectively essential roles in Hedgehog-mediated ventral neural patterning; genetic loss-of-function demonstrates an obligatory requirement for these three co-receptors in HH pathway activity in multiple tissues, including early cell fate specification and later motor neuron progenitor maintenance. Compound mouse genetic knockouts (single, double, triple mutants), neural patterning assays Developmental cell High 21664576
2011 Boc (with Cdon and Gas1) forms distinct receptor complexes with Ptch1; in cerebellar granule neuron progenitors, Boc, Cdon, and Gas1 are absolutely required for Hh-dependent proliferation, and a mutated Hh ligand that binds Ptch1 but not Boc/Cdon/Gas1 cannot activate Hh signaling, demonstrating that ligand binding to co-receptors is obligatory for signaling. Co-immunoprecipitation (Boc–Ptch1 complex), Hh binding mutant ligand, genetic knockout of all three co-receptors in CGNP proliferation assay Developmental cell High 21664577
2010 Boc modifies the holoprosencephaly (HPE) spectrum of Cdo mutant mice: Boc single mutants have no HPE, but Cdo;Boc double mutants display lobar HPE with craniofacial anomalies and defects in Shh target gene expression in the developing forebrain, identifying BOC as a silent HPE modifier gene. Mouse double knockout genetic epistasis, Shh target gene expression analysis Disease models & mechanisms High 21183473
2014 BOC associates with Ptch1 and promotes Shh-driven granule cell precursor (GCP) proliferation; mechanistically, Boc, through elevated Shh signaling, promotes high levels of DNA damage mediated by CyclinD1, which increases Ptch1 loss-of-heterozygosity and thereby drives medulloblastoma progression. Boc genetic knockout in medulloblastoma model, CyclinD1 manipulation, LOH analysis, proliferation assays Developmental cell High 25263791
2015 CDON and BOC utilize distinct molecular mechanisms in HH signal transduction: they have separate extracellular motifs required for HH promotion and distinct membrane attachment requirements, despite displaying functional redundancy in ventral neural patterning. In vivo gain-of-function (chick spinal cord electroporation) with domain deletion and swap mutants Developmental biology Medium 25848697
2016 BOC interacts with the non-receptor tyrosine kinase ABL through its putative SH2-binding domain and is phosphorylated in an ABL-dependent manner; BOC–ABL interaction is required for JNK activation and BOC-mediated promotion of neuronal differentiation and neurite outgrowth in P19 cells and cortical neural progenitor cells. Co-immunoprecipitation (BOC–ABL), ABL-binding defective BOC mutants, JNK activation assay, neurite length measurement in Boc−/− NPCs Cellular signalling Medium 27871935
2019 Shh induces Boc internalization into early endosomes; the endocytic adaptor Numb binds to Boc and is required for Boc internalization, Shh-mediated growth-cone turning in vitro, and commissural axon guidance in vivo. Boc binding to Shh is required for Ptch1 internalization; thus, Boc acts as a Shh-dependent endocytic platform gating Ptch1 internalization and Shh signaling in axon guidance. Endosome fractionation/live imaging of Boc internalization, Co-IP (Boc–Numb), Numb RNAi knockdown, in vitro growth-cone turning, in vivo commissural axon tracing Neuron High 31054872
2019 The Shh receptor Boc is important for myelination: Boc mutant mice exhibit transient decrease in oligodendroglial cell density, delayed myelination, lower myelin basic protein production, reduced callosal axon caliber, and impaired OPC differentiation during myelin repair, and Boc mutant microglia/macrophages show defective morphological transition in vivo. Boc knockout mouse analysis, immunostaining for oligodendroglial markers, MBP quantification, myelin repair assay Development Medium 31048318
2020 Ptch1/Boc and Ptch2/Gas1 form distinct hetero-complexes that mediate Smo de-repression with different kinetics and through distinct modes of Hedgehog ligand reception; Ptch1/Boc complex mediates primordial germ cell migration in mice. Compound mouse genetic knockouts, co-immunoprecipitation of Ptch1/Boc and Ptch2/Gas1 complexes, PGC migration assays, phospho-Creb/Src signaling analysis Nature communications Medium 32332736
2020 BOC acts as a multi-functional regulator of HH signaling during craniofacial development: Boc deletion results in facial widening correlated with increased HH target gene expression, and Boc deletion in a Gas1-null background partially rescues craniofacial defects of Gas1 single mutants, demonstrating tissue-specific HH-promoting or HH-restraining roles for BOC. Single and compound mouse genetic knockouts, HH target gene expression analysis, craniofacial morphometry Development Medium 33060130
2021 A Dispatched (DISP)–BOC/CDON co-receptor complex functions in Shh ligand-producing cells to promote cytoneme occurrence and facilitate ligand delivery; Myosin 10 promotes vesicular transport of Shh in cytonemes and is required for SHH gradient organization in the neural tube. Co-immunoprecipitation (DISP–BOC complex), Myo10 genetic knockout mouse neural tube analysis, live-cell imaging of cytonemes, rapid signal-response assay eLife Medium 33570491
2015 Mice lacking the HH co-receptor BOC display age-related overweight and excess white adipose tissue; cultured Boc−/− mouse embryo fibroblasts show enhanced adipogenesis and reduced HH pathway target gene expression, placing BOC as a positive regulator of HH signaling that inhibits adipogenesis. Boc knockout mouse adiposity analysis, in vitro adipogenesis assay in MEFs, HH target gene expression Diabetes Medium 25576054
2013 Shh/Boc signaling is required for sustained generation of ipsilateral-projecting retinal ganglion cells (iRGCs): in Boc−/− mice, the number of Zic2-positive iRGCs is reduced while Islet2/Shh-positive RGCs increase, indicating Boc is required to sustain Zic2 expression likely by regulating Shh signaling levels from neighboring contralateral RGCs. Boc knockout mouse analysis, immunostaining for Zic2/Islet2 markers, in vivo electroporation of Shh, Zic2, and Boc, retinal projection analysis The Journal of neuroscience Medium 23678105
2005 Zebrafish BOC functions as an axon-guidance molecule for dorsoventrally projecting axon tracts: morpholino knockdown of boc causes selective defects in ventrally projecting axons arising from the presumptive telencephalon. Antisense morpholino knockdown in zebrafish, axon tract immunostaining The Journal of comparative neurology Medium 15776441
2017 Missense BOC variants identified in holoprosencephaly patients have either loss- or gain-of-function properties in cell-based SHH signaling assays, confirming BOC as a modifier gene whose variant alleles alter SHH pathway activity. Cell-based SHH signaling assays with patient-derived BOC variant proteins Human mutation Medium 28677295
2019 A novel BOC-PLAG1 fusion gene was identified in lipoblastoma, in which the constitutively active BOC promoter drives overexpression of PLAG1, establishing a mechanism for PLAG1 activation in this tumor. 5' RACE, RNA sequencing, qRT-PCR Biochemical and biophysical research communications Low 30857637

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 The cell surface membrane proteins Cdo and Boc are components and targets of the Hedgehog signaling pathway and feedback network in mice. Developmental cell 298 16647304
2006 Boc is a receptor for sonic hedgehog in the guidance of commissural axons. Nature 242 17086203
2011 Overlapping roles and collective requirement for the coreceptors GAS1, CDO, and BOC in SHH pathway function. Developmental cell 227 21664576
2011 Boc and Gas1 each form distinct Shh receptor complexes with Ptch1 and are required for Shh-mediated cell proliferation. Developmental cell 198 21664577
2002 BOC, an Ig superfamily member, associates with CDO to positively regulate myogenic differentiation. The EMBO journal 125 11782431
2013 Enantioconvergent cross-couplings of racemic alkylmetal reagents with unactivated secondary alkyl electrophiles: catalytic asymmetric Negishi α-alkylations of N-Boc-pyrrolidine. Journal of the American Chemical Society 118 23869442
2007 Cyclosporin H, Boc-MLF and Boc-FLFLF are antagonists that preferentially inhibit activity triggered through the formyl peptide receptor. Inflammation 115 17687636
2007 Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies. Journal of the American Chemical Society 110 18085777
1987 Autoradiography of CCK receptors in the rat brain using [(3)H]Boc[Nle(28)(31)]CCK(27)-(33) and [(125)I]bolton-hunter CCK(8). Functional significance of subregional distributions. Neurochemistry international 72 20501122
2010 Segregation of ipsilateral retinal ganglion cell axons at the optic chiasm requires the Shh receptor Boc. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 20053908
2016 Boc3Arg-Linked Ligands Induce Degradation by Localizing Target Proteins to the 20S Proteasome. ACS chemical biology 64 27704767
2012 Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif. Developmental biology 64 23276604
2010 Drosophila Boi limits Hedgehog levels to suppress follicle stem cell proliferation. The Journal of cell biology 63 21098113
2010 Formation of arginine modifications in a model system of Nα-tert-butoxycarbonyl (Boc)-arginine with methylglyoxal. Journal of agricultural and food chemistry 62 21126021
2006 Mechanistic studies of peroxynitrite-mediated tyrosine nitration in membranes using the hydrophobic probe N-t-BOC-L-tyrosine tert-butyl ester. Biochemistry 62 16734418
1994 Effects of BOC-CCK-4 and L 365.260 on cortical 5-HT release in guinea-pigs on exposure to the elevated plus maze. Neuropharmacology 61 7527129
1989 Alpha-helix and mixed 3(10)/alpha-helix in cocrystallized conformers of Boc-Aib-Val-Aib-Aib-Val-Val-Val-Aib-Val-Aib-OMe. Proceedings of the National Academy of Sciences of the United States of America 61 2915976
2004 Synthesis of all nineteen appropriately protected chiral alpha-hydroxy acid equivalents of the alpha-amino acids for Boc solid-phase depsi-peptide synthesis. Organic letters 60 14961607
2010 Boc modifies the holoprosencephaly spectrum of Cdo mutant mice. Disease models & mechanisms 57 21183473
2010 All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner. The Journal of biological chemistry 54 20519495
1986 Parallel packing of alpha-helices in crystals of the zervamicin IIA analog Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe.2H2O. Proceedings of the National Academy of Sciences of the United States of America 53 2432594
2021 Cytoneme delivery of Sonic Hedgehog from ligand-producing cells requires Myosin 10 and a Dispatched-BOC/CDON co-receptor complex. eLife 49 33570491
2004 Aza-amino acid scan for rapid identification of secondary structure based on the application of N-Boc-aza(1)-dipeptides in peptide synthesis. Journal of the American Chemical Society 49 15161304
2014 The Shh receptor Boc promotes progression of early medulloblastoma to advanced tumors. Developmental cell 48 25263791
1988 Aqueous channels within apolar peptide aggregates: solvated helix of the alpha-aminoisobutyric acid (Aib)-containing peptide Boc-(Aib-Ala-Leu)3-Aib-OMe.2H2O.CH3OH in crystals. Proceedings of the National Academy of Sciences of the United States of America 47 2448772
2001 Kinetics and mechanism of the (-)-sparteine-mediated deprotonation of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine. Journal of the American Chemical Society 44 11457318
2010 Ihog and Boi are essential for Hedgehog signaling in Drosophila. Neural development 42 21044292
1999 BOC-CCK-4, CCK(B)receptor agonist, antagonizes anxiolytic-like action of morphine in elevated plus-maze. Neuropeptides 40 10657473
2002 Expression of the boc gene during murine embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 39 11891987
2013 Shh/Boc signaling is required for sustained generation of ipsilateral projecting ganglion cells in the mouse retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 23678105
2020 The hedgehog co-receptor BOC differentially regulates SHH signaling during craniofacial development. Development (Cambridge, England) 34 33060130
2012 Efficient synthesis of glycopeptide-α-thioesters with a high-mannose type oligosaccharide by means of tert-Boc-solid phase peptide synthesis. Carbohydrate research 34 23149340
1993 Design of peptides: crystal and molecular structure of a 3(10)-helical peptide N-Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro-Phe-L-Val-OCH3. Biopolymers 34 8467067
1991 Boc-CCK-4 derivatives containing side-chain ureas as potent and selective CCK-a receptor agonists. Journal of medicinal chemistry 34 1716682
1993 Peptide design 3(10)-helical conformation of a linear pentapeptide containing two dehydrophenylalanines, Boc-Gly-delta ZPhe-Leu-delta ZPhe-Ala-NHCH3. Biopolymers 31 8485295
1985 [3H] Boc [Nle28, 31]CCK27-33, a new highly labelled ligand for CCK receptors: binding on brain and on pancreas. Life sciences 31 3001463
2019 Boc Acts via Numb as a Shh-Dependent Endocytic Platform for Ptch1 Internalization and Shh-Mediated Axon Guidance. Neuron 30 31054872
2006 boc-Aspartyl(OMe)-fluoromethylketone attenuates mitochondrial release of cytochrome c and delays brain tissue loss after traumatic brain injury in rats. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 30 16736044
2007 Synthesis and evaluation of the antiproliferative activities of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine. Journal of medicinal chemistry 27 17990847
2019 Identification of a novel BOC-PLAG1 fusion gene in a case of lipoblastoma. Biochemical and biophysical research communications 26 30857637
2015 The Arabidopsis RING Domain Protein BOI Inhibits Flowering via CO-dependent and CO-independent Mechanisms. Molecular plant 26 26298008
2014 Boc modifies the spectrum of holoprosencephaly in the absence of Gas1 function. Biology open 26 25063195
2012 Cdon and Boc: Two transmembrane proteins implicated in cell-cell communication. The international journal of biochemistry & cell biology 26 22326621
1999 Fission yeast Pob1p, which is homologous to budding yeast Boi proteins and exhibits subcellular localization close to actin patches, is essential for cell elongation and separation. Molecular biology of the cell 26 10436025
1995 Synthesis, and crystal and molecular structure of the 3(10)-helical alpha,beta-dehydro pentapeptide Boc-Leu-Phe-Ala-delta Phe-Leu-OMe. Biopolymers 26 7696560
1992 Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP. Immunology 26 1282494
2011 Discovery of novel (4-piperidinyl)-piperazines as potent and orally active acetyl-CoA carboxylase 1/2 non-selective inhibitors: F-Boc and triF-Boc groups are acid-stable bioisosteres for the Boc group. Bioorganic & medicinal chemistry 25 21324704
2015 A highly efficient Mukaiyama-Mannich reaction of N-Boc isatin ketimines and other active cyclic ketimines using difluoroenol silyl ethers catalyzed by Ph3PAuOTf. Organic & biomolecular chemistry 24 26443467
2009 7-(O)-Carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine: a novel compound capable of inducing cell death in epithelial ovarian cancer stem cells. Cancer biology & therapy 24 19738422
2005 BOC, brother of CDO, is a dorsoventral axon-guidance molecule in the embryonic vertebrate brain. The Journal of comparative neurology 24 15776441
1988 Monoclinic polymorph of Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe(anhydrous). Parallel packing of 3(10)-/alpha-helices and a transition of helix type. International journal of peptide and protein research 24 3079530
2016 A Sonic hedgehog coreceptor, BOC regulates neuronal differentiation and neurite outgrowth via interaction with ABL and JNK activation. Cellular signalling 23 27871935
2020 Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration. Nature communications 22 32332736
2019 A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific, On-Resin Ozonolysis to Install the Kynurenine Residue. Chemistry (Weinheim an der Bergstrasse, Germany) 22 31429133
1992 Crystal structure and conformation of a highly constrained linear tetrapeptide Boc-Leu-dehydro Phe-Ala-Leu-OCH3. International journal of peptide and protein research 22 1399261
1989 Automated synthesis of a C-terminal photoprobe using combined Fmoc and t-Boc synthesis strategies on a single automated peptide synthesizer. Peptide research 22 2520777
2017 BOC is a modifier gene in holoprosencephaly. Human mutation 21 28677295
2006 Boc-lysinated-betulonic acid: a potent, anti-prostate cancer agent. Bioorganic & medicinal chemistry 20 16777417
1992 Disulfide bond as peptide-resin linkage in Boc-Bzl SPPS, for potential biochemical applications. Peptide research 20 1330111
2016 HF-Free Boc Synthesis of Peptide Thioesters for Ligation and Cyclization. Angewandte Chemie (International ed. in English) 19 27654901
2015 Distinct structural requirements for CDON and BOC in the promotion of Hedgehog signaling. Developmental biology 19 25848697
2020 Design, characterization, and evaluation of antibacterial gels, Boc-D-Phe-γ4-L-Phe-PEA/chitosan and Boc-L-Phe-γ4-L-Phe-PEA/chitosan, for biomaterial-related infections. Materials science & engineering. C, Materials for biological applications 18 32204079
2019 The Shh receptor Boc is important for myelin formation and repair. Development (Cambridge, England) 18 31048318
2001 PNA synthesis using a novel Boc/acyl protecting group strategy. Journal of peptide science : an official publication of the European Peptide Society 18 11548056
1989 Regularly alternating L,D-peptides. I. The double-stranded left-handed antiparallel beta-helix in the structure of Boc-(L-Val-D-Val)4-OMe. Biopolymers 18 2720104
2011 Synthesis and oligomerization of Fmoc/Boc-protected PNA monomers of 2,6-diaminopurine, 2-aminopurine and thymine. Organic & biomolecular chemistry 17 22159214
2006 Pharmacokinetics and metabolism in mice of IDN 5390 (13-(N-Boc-3-i-butylisoserinoyl)-C-7,8-seco-10-deacetylbaccatin III), a new oral c-seco-taxane derivative with antiangiogenic property effective on paclitaxel-resistant tumors. Drug metabolism and disposition: the biological fate of chemicals 17 16963486
2005 Semisynthesis of human ghrelin: condensation of a Boc-protected recombinant peptide with a synthetic O-acylated fragment. Biopolymers 17 16049959
1988 Aggregation studies in crystals of apolar helical peptides: Boc-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe. International journal of peptide and protein research 17 3246478
2021 Association of sonic hedgehog signaling pathway genes IHH, BOC, RAB23a and MIR195-5p, MIR509-3-5p, MIR6738-3p with gastric cancer stage. Scientific reports 16 33811245
2021 Synthesis of N-Boc-α-amino Acids from Carbon Dioxide by Electrochemical Carboxylation of N-Boc-α-aminosulfones. The Journal of organic chemistry 16 34550701
2022 5-O-(N-Boc-l-Alanine)-Renieramycin T Induces Cancer Stem Cell Apoptosis via Targeting Akt Signaling. Marine drugs 15 35447911
2020 Palladium-mediated Suzuki-Miyaura Cross-Coupling Reaction of Potassium Boc-protected aminomethyltrifluoroborate with DNA-Conjugated aryl bromides for DNA-Encoded chemical library synthesis. Biochemical and biophysical research communications 15 32376009
2015 Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor boc. Diabetes 15 25576054
1990 Correlation between phospholipid breakdown, intracellular calcium mobilization and enzyme secretion in rat pancreatic acini treated with Boc-[Nle28, Nle31]-CCK-7 and JMV180, two cholecystokinin analogues. Cellular signalling 15 1701321
2021 Glypicans define unique roles for the Hedgehog co-receptors boi and ihog in cytoneme-mediated gradient formation. eLife 14 34355694
2020 Drug-interactive mPEG-b-PLA-Phe(Boc) micelles enhance the tolerance and anti-tumor efficacy of docetaxel. Drug delivery 14 32003299
2006 Mixed-sequence pyrrolidine-amide oligonucleotide mimics: Boc(Z) synthesis and DNA/RNA binding properties. Organic & biomolecular chemistry 14 17205168
1995 CCK-A receptor selective antagonists derived from the CCK-A receptor selective tetrapeptide agonist Boc-Trp-Lys(Tac)-Asp-MePhe-NH2 (A-71623). Journal of medicinal chemistry 14 7837233
2022 Chemical Synthesis of Proteins with Base-Labile Posttranslational Modifications Enabled by a Boc-SPPS Based General Strategy Towards Peptide C-Terminal Salicylaldehyde Esters. Angewandte Chemie (International ed. in English) 13 36344442
2015 Rapid Synthesis of Boc-2',6'-dimethyl-l-tyrosine and Derivatives and Incorporation into Opioid Peptidomimetics. ACS medicinal chemistry letters 13 26713104
2012 The Drosophila WIF1 homolog Shifted maintains glypican-independent Hedgehog signaling and interacts with the Hedgehog co-receptors Ihog and Boi. Development (Cambridge, England) 13 23154411
2011 Anti-thyroid cancer properties of a novel isoflavone derivative, 7-(O)-carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine in vitro and in vivo. The Journal of steroid biochemistry and molecular biology 13 21600982
2005 Dynamic kinetic resolution of N-Boc-2-lithiopyrrolidine. Chemical communications (Cambridge, England) 13 15959592
1992 Helix packing of leucine-rich peptides: a parallel leucine ladder in the structure of Boc-Aib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe. Proteins 13 1579566
2021 Differential Expression of BOC, SPOCK2, and GJD3 Is Associated with Brain Metastasis of ER-Negative Breast Cancers. Cancers 12 34203581
2020 D-Peptide analogues of Boc-Phe-Leu-Phe-Leu-Phe-COOH induce neovascularization via endothelial N-formyl peptide receptor 3. Angiogenesis 12 32152757
2020 Mild deprotection of the N-tert-butyloxycarbonyl (N-Boc) group using oxalyl chloride. RSC advances 12 33456769
2007 Incorporation of the hydrophobic probe N-t-BOC-L-tyrosine tert-butyl ester to red blood cell membranes to study peroxynitrite-dependent reactions. Chemical research in toxicology 12 17941688
2004 Highly enantioselective reaction of lithiated N-Boc-thiazolidine: a new chiral formyl anion equivalent. Organic & biomolecular chemistry 12 15280949
2003 Overexpression of the immunoglobulin superfamily members CDO and BOC enhances differentiation of the human rhabdomyosarcoma cell line RD. Molecular carcinogenesis 12 12720294
1992 Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N epsilon)-amide residues. Journal of medicinal chemistry 12 1375964
2021 BOC-PLAG1, a new fusion gene of pleomorphic adenoma: Identified in a fine-needle aspirate by RNA next-generation sequencing. Diagnostic cytopathology 11 33710800
2012 Sonic hedgehog, BOC, and synaptic development: new players for an old game. Neuron 11 22445332
2012 Growth inhibition of human thyroid carcinoma and goiter cells in vitro by the isoflavone derivative 7-(O)-carboxymethyl daidzein conjugated to N-t-boc-hexylenediamine. Thyroid : official journal of the American Thyroid Association 11 22799572
1996 Helix termination and chain reversal: crystal and molecular structure of the alpha, beta-dehydrooctapeptide Boc-Val-DeltaPhe-Phe-Ala-Leu-Ala-DeltaPhe-Leu-OH. Journal of biomolecular structure & dynamics 11 8906884
2018 Characterization of a Carbonyl Reductase from Rhodococcus erythropolis WZ010 and Its Variant Y54F for Asymmetric Synthesis of (S)-N-Boc-3-Hydroxypiperidine. Molecules (Basel, Switzerland) 10 30487432
2008 Tyrosine nitration, dimerization, and hydroxylation by peroxynitrite in membranes as studied by the hydrophobic probe N-t-BOC-l-tyrosine tert-butyl ester. Methods in enzymology 10 18554537
2003 Effects of intrathecal administration of a cell permeant caspase inhibitor, boc-D-fluoromethylketone (BDFMK), on behavioral deficits following spinal cord ischemia: a dose-response analysis. Brain research 10 12493605
2003 Clinical and immunomodulatory effects of fun-boi, an herbal medicine, on collagen-induced arthritis in vivo. Clinical and experimental rheumatology 10 12673890