Comparison of cyclic and linear analogs of vasoactive intestinal peptide.
A series of i-->i + 4 side-chain to side-chain lactam analogs of vasoactive intestinal peptide has been prepared in order to study the effect of cyclization on biological activity. In vitro, on guinea pig tracheal smooth muscle and on human bronchial tissue, approximately half of the cyclic analogs showed increased potency and half were decreased over the linear analogs. Several cyclic compounds were between 10- and 20-fold more potent and one was 290-fold more potent than the linear species. In vivo, in guinea pigs, the cyclic compounds showed increased potency by up to 70-fold and significantly enhanced duration of action as compared to linear compounds.
Bolin
D R
DR
Roche Research Center, Hoffman-La Roche, Inc., Nutley, NJ 07110, USA.
Cottrell
J
J
Garippa
R
R
Rinaldi
N
N
Senda
R
R
Simko
B
B
O'Donnell
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D002942:Circular Dichroism; D003500:Cyclization; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D017433:Protein Structure, Secondary; D014132:Trachea / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000494:pharmacology
D014660:Vasoactive Intestinal Peptide