A novel beta-turn mimic useful for mapping the unknown topology of peptide receptors.
Ethers of cis or trans D-4-hydroxyproline (Hype), adjacent to octahydroindole-carboxylic acid (Oic), introduce a beta-turn into the backbone of peptides when positioned respectively at the i+1 and i+2 position of the turn. This is confirmed by NMR experiments performed on a model tetrapeptide in water. Synthetic alteration of the ether group allows simple probing of the steric limits and electrostatic potential of a receptor binding site, a technique applied successfully to the bradykinin receptor.
Kyle
D J
DJ
Nova Pharmaceutical Corporation, Baltimore, MD 21224.
Green
L M
LM
Blake
P R
PR
Smithwick
D
D
Summers
M F
MF
D000595:Amino Acid Sequence; D001920:Bradykinin; D004987:Ethers; D006909:Hydroxyproline / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010449:Peptide Mapping / Q000379:methods*; D017433:Protein Structure, Secondary; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000737:chemistry*
D004987:Ethers; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D006909:Hydroxyproline; D001920:Bradykinin