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Comparison of insect kinin analogs with cis-peptide bond motif 4-aminopyroglutamate identifies optimal stereochemistry for diuretic activity.
- Source :
-
Biopolymers [Biopolymers] 2007; Vol. 88 (1), pp. 1-7. - Publication Year :
- 2007
-
Abstract
- The insect kinins are present in a wide variety of insects and function as potent diuretic peptides, though they are subject to rapid degradation by internal peptidases. Insect kinin analogs incorporating stereochemical variants of (2S,4S)-4-aminopyroglutamate (APy), a cis-peptide bond motif, demonstrate significant activity in a cricket diuretic assay. Insect kinin analogs containing (2R,4R)-APy, (2S,4R)-APy and (2S,4S)-APy are essentially equipotent on an insect diuretic assay, with EC(50) values of about 10(-7)M, whereas the (2R,4S)-APy analog is at least 10-fold more potent (EC(50) = 7 x 10(-9)M). Conformational studies in aqueous solution indicate that the (2R,4S)-APy analog is considerably more flexible than the other three variants, which may explain its greater potency. The work identifies the optimal stereochemistry for the APy scaffold with which to design biostable, peptidomimetic analogs with the potential to disrupt critical insect kinin-regulated processes in insects.
- Subjects :
- Amino Acid Motifs
Animals
Biopolymers chemistry
Diuresis drug effects
Drug Design
Female
Gryllidae chemistry
Gryllidae drug effects
Gryllidae genetics
In Vitro Techniques
Insect Proteins genetics
Insect Proteins pharmacology
Insecta chemistry
Insecta drug effects
Insecta genetics
Kinins genetics
Kinins pharmacology
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Protein Conformation
Pyrrolidonecarboxylic Acid chemistry
Stereoisomerism
Insect Proteins chemistry
Kinins chemistry
Pyrrolidonecarboxylic Acid analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3525
- Volume :
- 88
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biopolymers
- Publication Type :
- Academic Journal
- Accession number :
- 17054115
- Full Text :
- https://doi.org/10.1002/bip.20613