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Molecular recognition between oligopeptides and nucleic acids. DNA sequence specificity and binding properties of an acridine‐linked netropsin hybrid ligand
Author(s) -
Bailly Christian,
Helbecque Nicole,
Hénichart JeanPierre,
Colson Pierre,
Houssier Claude,
Rao K. Ekambareswara,
Shea Regan G.,
Lown J. William
Publication year - 1990
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.300030103
Subject(s) - netropsin , moiety , acridine , dna , stereochemistry , chemistry , intercalation (chemistry) , binding site , oligopeptide , circular dichroism , footprinting , nucleic acid , peptide , biochemistry , minor groove , organic chemistry , base sequence
Abstract The binding to DNA of a mixed function ligand (NETGA) is described, in which a potential intercalating group, an acridine moiety, is incorporated at the carboxyl terminus of the minor groove binding oligopeptide netropsin skeleton. Scatchard analysis of absorption data provided evidence of two modes of binding to DNA with K 1 = 9.1 × 10 5 M −1 at low r values (0.003–0.1), and a binding site size n = 10, indicative of binding of both moeities. At high binding ratios (>0.1), K 2 = 0.9 × 10 5 M −1 and n = 5 corresponding to external binding. Complementary strand MPE footprinting on a pBR322 restriction fragment showed NETGA binds to 5′‐AAAT like netropsin. It causes enhanced cleavage by MPE, particularly at G‐C rich sequences and remote from the preferred binding sites. Viscometry measurements provided evidence for biphasic modes of the two binding portions of NETGA. Fluorescence polarization and linear dichroism measurements were in accord with distinct modes of interaction of the acridine (intercalation) and oligopeptide (minor groove binding) portions of NETGA. LD measurments of NETGA indicate that the oligopeptide moiety (netropsin‐like) has an orientation typical of minor groove binders, whereas the degree of intercalation of the acridine group is decreased by association of the oligopeptide moiety.