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Synthesis and activity of dimeric bradykinin antagonists containing diaminodicarboxylic acid bridge residues
Author(s) -
Lange Meinolf,
Cuthbertson Alan S.,
Towart Robertson,
Fischer Peter M.
Publication year - 1998
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/(sici)1099-1387(199806)4:4<289::aid-psc146>3.0.co;2-t
Subject(s) - chemistry , bradykinin , thioether , stereochemistry , cysteine , bradykinin receptor , residue (chemistry) , peptide , cystine , solid phase synthesis , ligand (biochemistry) , alkyl , amino acid , receptor , biochemistry , enzyme , organic chemistry
Enhancement of a ligand's interaction with a receptor through presenting the ligand in multimeric form is a topic of general interest. Thus dimerization of single‐chain bradykinin antagonist peptides has previously been shown to be beneficial in terms of potency and duration of action. While crosslinking polypeptides at terminal positions using suitable dicarboxylic acids and diamines is comparatively straightforward synthetically, internal dimerizations are usually achieved through oxidation or double S ‐alkylations of cysteine residues, resulting in metabolically unfavourable disulphide and thioether cross‐links. Using suitably modified standard solid‐phase peptide synthesis protocols, dimeric bradykinin antagonist peptides [H‐( d ‐Arg)‐Arg‐Pro‐Hyp‐Gly‐Phe] 2 ‐X‐[( d ‐Phe)‐Leu‐Arg‐OH] 2 were synthesized where X corresponds to a l , l ‐2,7‐diaminosuberic or l , l ‐2,9‐diaminosebacic acid residue, respectively. The biological activity of these peptides was comparable to that of conventional dimeric bradykinin antagonists cross‐linked through cystine or bis(succinimido)alkyl bridges. © 1998 European Peptide Society and John Wiley & Sons, Ltd.