Paired Utility of Aza-Amino Acyl Proline and Indolizidinone Amino Acid Residues for Peptide Mimicry: Conception of Prostaglandin F2α Receptor Allosteric Modulators That Delay Preterm Birth

Peptide mimicry employing a combination
of aza-amino acyl proline
and indolizidinone residues has been used to develop allosteric modulators
of the prostaglandin F2α receptor. The systematic study of the N-terminal phenylacetyl moiety and the conformation and
side chain functions of the central turn dipeptide residue has demonstrated
the sensitive relationships between modulator activity and topology.
Examination of aza-Gly-Pro and aza-Phe-Pro analogs 2a and 2b in a murine preterm labor model featuring treatment
with lipopolysaccharide demonstrated their capacity to extend significantly
(>20 h) the average time of delivery offering new prototypes for
delaying
premature birth.