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Selective Modulation of DNA Polymerase Activity by Fixed‐Conformation Nucleoside Analogues
Author(s) -
Eoff Robert L.,
McGrath Colleen E.,
Maddukuri Leena,
SalamancaPinzón S. Giovanna,
Marquez Victor E.,
Marnett Lawrence J.,
Guengerich F. Peter,
Egli Martin
Publication year - 2010
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201003168
Subject(s) - dna polymerase , polymerase , dna , microbiology and biotechnology , chemistry , deoxyadenosine , nucleoside , stereochemistry , dna replication , biology , biochemistry
Picking a pucker! Fixed‐conformation North (N)‐ and South (S)‐methanocarba‐2′‐deoxyadenosine‐triphosphate (MC‐dATP) have different effects in DNA strand extension catalyzed by HIV‐1 RT and three human Y‐family DNA polymerases (pols). All of the polymerases tested preferred the N‐oriented furanose geometry, though pol η could insert both pucker mimics. The growth of malignant breast cancer cells overexpressing pol ι was more severely inhibited by N‐MC‐dATP than that of nonmalignant breast cells.