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STa peptide analogs for probing guanylyl cyclase C
Author(s) -
Tian Xiaobing,
Michal Allison M.,
Li Peng,
Wolfe Henry R.,
Waldman Scott A.,
Wickstrom Eric
Publication year - 2008
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21045
Subject(s) - chemistry , peptide , residue (chemistry) , peptide synthesis , preprint , oligopeptide , disulfide bond , amino acid , soluble guanylyl cyclase , biochemistry , stereochemistry , receptor , guanylate cyclase , world wide web , computer science
Guanylyl cyclase C (GC‐C), universally overexpressed on primary and metastatic colorectal carcinoma cells, is activated by endogenous ligands, guanylin, and uroguanylin, and by exogenous 18‐residue heat‐stable enterotoxins (STa) produced by diarrheagenic bacteria. Two 12‐residue STa analogs with alternate combinations of two interlocked disulfide bonds, peptides 3 and 6 , were synthesized by orthogonal solid phase synthesis routes. Peptides 3 and 6 bound GC‐C with a rank order potency of STa > peptide 3 > peptide 6 . Peptides 3 and 6 behaved as agonists in stimulating cGMP production. The results reveal that the toxic domain of STa can be reduced to 12 amino acids. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 713–723, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com