Structure-activity analysis of a Conus peptide blocker of N-type neuronal calcium channels.

Abstract:

:The synthetic peptide SNX-111 corresponding to the sequence of the omega-conopeptide MVIIA from the venom of the marine snail Conus magus is a highly potent and selective antagonist of N-type calcium channels. We have synthesized and characterized a large number of analogs of SNX-111 in order to elucidate the structural features of the peptide involved in blocking N-type calcium channels. Comparison of the binding of SNX-111 and its analogs to rat brain synaptosomal membranes rich in N-type channels revealed that, among the four lysines and two arginines in the molecule, lysine in position 2 and arginines at position 10 and 21 are important for the interaction of SNX-111 with N-type channels. The importance of the middle segment from residues 9 through 14 for this binding interaction was revealed by substitution of the individual residues as well as by the construction of hybrid peptides in which the residues 9-12 in SNX-111 and another conopeptide, SNX-183, corresponding to a peptide SVIB from Conus striatus, were interchanged. Introduction of the sequence SRLM from SNX-111 in place of RKTS in position 9-12 in SNX-183 resulted in a 38-fold increase in affinity.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Nadasdi L,Yamashiro D,Chung D,Tarczy-Hornoch K,Adriaenssens P,Ramachandran J

doi

10.1021/bi00025a013

subject

Has Abstract

pub_date

1995-06-27 00:00:00

pages

8076-81

issue

25

eissn

0006-2960

issn

1520-4995

journal_volume

34

pub_type

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