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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM074401-01
Application #
6836163
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Basavappa, Ravi
Project Start
2004-09-01
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$42,976
Indirect Cost
Name
Yale University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Kritzer, Joshua A; Luedtke, Nathan W (2005) Chemical biology: innovative solutions for diverse challenges. Chem Biol 12:617-20
Luedtke, Nathan W; Schepartz, Alanna (2005) Lanthanide-mediated phosphoester hydrolysis and phosphate elimination from phosphopeptides. Chem Commun (Camb) :5426-8
Kritzer, Joshua A; Luedtke, Nathan W; Harker, Elizabeth A et al. (2005) A rapid library screen for tailoring beta-peptide structure and function. J Am Chem Soc 127:14584-5