Synthesis and Structural Confirmation of PyHOPO and its Applicability in Racemization Reduction in Solid-Phase Peptide Synthesis

Abstract

In the current work, PyHOPO was synthesized and well characterized by single ray XRD. The crystal structure unambiguously confirmed the presence of a P-O-N bond rather than a P-O-C bond. The conversion of HOPO to PyHOPO elongates the N O bond length thereby changing the electron density distribution, as evidenced by electrostatic mapping. This highlights the phosphorus atom's electron-donating nature toward the HOPO moiety. PyHOPO was used to prepare pentapeptide H-Tyr-Ser-Ser-Phe-Leu-NH 2 . PyHOPO was then evaluated for racemization study. Racemization was studied in the case of Ser, His and Cys upon incorporation in a tripeptide (Gly-X-Phe-NH 2 ; where X = Ser, His, Cys). For the study, it was found that there was no racemization in all the three cases when PyHOPO was used as coupling reagent. • Synthesis of PyHOPO with good yield. • Confirmation of P-O-N bond formation instead of P-O-C by X-ray crystallography. • Formation of PyHOPO shifts the electron density distribution of HOPO when alone. • Successful synthesis of H-Tyr-Ser-Ser-Phe-Leu-NH 2 . • No racemization found in any case of tripeptide H-Gly-X-Phe-NH 2 (where X = Ser, His, Cys).