It is proposed to carry out extensive nuclear magnetic resonance studies of nucleic acids and their drug complexes in solution. These experimental studies along with theoretical modelling will enable to delineate the intimate details of their molecular geometry and stereodynamics. A detailed understanding of these dynamic spatial structures is fundamental to comprehend the function and mechanism of many drugs which bind and intercalate with nucleic acids. It is hoped that the information will be of assistance in the development of new drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM029787-14
Application #
3277433
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1982-09-15
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
14
Fiscal Year
1985
Total Cost
Indirect Cost
Name
State University of New York at Albany
Department
Type
Schools of Arts and Sciences
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12222
Ulyanov, N B; Sarma, M H; Zhurkin, V B et al. (1993) Decreased interstrand H2-H1' distance in the GC-rich part of the duplex d(CCTCAAACTCC).d(GGAGTTTGAGG) in solution at low temperature: proton nuclear magnetic resonance investigation. Biochemistry 32:6875-83
Ulyanov, N B; Gorin, A A; Zhurkin, V B et al. (1992) Systematic study of nuclear Overhauser effects vis-a-vis local helical parameters, sugar puckers, and glycosidic torsions in B DNA: insensitivity of NOE to local transitions in B DNA oligonucleotides due to internal structural compensations. Biochemistry 31:3918-30
Luo, J; Sarma, M H; Yuan, R D et al. (1992) NMR study of self-paired parallel duplex of d(AAAAACCCCC) in solution. FEBS Lett 306:223-8
Sarma, M H; Luo, J; Umemoto, K et al. (1992) Tetraplex formation of d(GGGGGTTTTT): 1H NMR study in solution. J Biomol Struct Dyn 9:1131-53
Umemoto, K; Sarma, M H; Gupta, G et al. (1990) Effect of the methyl group on DNA bending and curvature: structure of d(GA4U4C)2 in solution. Biochemistry 29:4714-22
Sarma, M H; Umemoto, K; Gupta, G et al. (1990) In search of a Hoogsteen base paired DNA duplex in aqueous solution. J Biomol Struct Dyn 8:461-82
Sarma, M H; Gupta, G; Garcia, A E et al. (1990) Quantitative structure of a complex between a minor-groove-specific drug and a bent DNA decamer duplex: use of 2D NMR data and NOESY constrained energy minimization. Biochemistry 29:4723-34
Sarma, M H; Gupta, G; Sarma, R H (1988) Structure of a bent DNA: two-dimensional NMR studies on d(GAAAATTTTC)2. Biochemistry 27:3423-32
Garcia, A E; Gupta, G; Sarma, M H et al. (1988) Stability and motion of a hairpin and the corresponding mismatched duplex: a theoretical exploration using molecular mechanics and normal mode analysis of 2D NMR results on d(GCCGCAGC). J Biomol Struct Dyn 6:525-42
Gupta, G; Sarma, M H; Sarma, R H (1988) On the question of DNA bending: two-dimensional NMR studies on d(GTTTTAAAAC)2 in solution. Biochemistry 27:7909-19

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