Assembly of Hydrolytic PeptideMetalloPorphyrin Complexes

Yale University, New Haven CT

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Novel peptide-porphyrin-lanthanide ternary complexes are proposed for the rapid and selective hydrolysis of human telomeric DNA. Protoporhyrin IX is presented as a unique, and underutilized, scaffold for the assembly of multicomponent combinatorial libraries. Libraries of peptide-porphyrin conjugates will be synthesized and screened for their ability to bind to a telomeric quadruplex DNA with high affinity and high specificity. In parallel to this, porphyrin-lanthanide complexes that hydrolytically cleave telomeric DNA will also be developed. The diverse functional groups present on protoporphyrin IX will allow for the synthesis of peptide-porphyrin-lanthanide ternary complexes that should retain both high telomere affinity/specificity as well as hydrolytic activity. These complexes, once characterized, should provide new insight into the basic principals involved in telomere recognition and hydrolysis, and may also provide new tools to study telomere function. [unreadable] [unreadable]