Investigation of the structure/activity relationship of human calcitonin gene-related peptide (CGRP).
The biological activities of calcitonin gene-related peptide (CGRP) enzymic digest fragments, chemically modified products and beta-CGRP have been compared to that of intact alpha-CGRP on rat isolated paired atria. Tryptic and chymotryptic digests both produced inactive fragments. Acetylation of the N-terminal amino acid (Alanine) or either of Lys 24 or Lys 35, resulted in reduced, but measurable, biological activity. Destruction of the disulphide bridge between Cys 2 and Cys 7 abolished biological activity. Substitution of several amino acids, Asp 3, Val 22 and Asn 25, with Asn, Met and Ser respectively (beta-CGRP), produced a peptide with similar biological activity to alpha-CGRP.
D000596:Amino Acids; D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin; D004220:Disulfides / Q000032:analysis; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014357:Trypsin
D000596:Amino Acids; D004220:Disulfides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D002918:Chymotrypsin; D014357:Trypsin; D015740:Calcitonin Gene-Related Peptide