With the advancement in 2D-NMR methodologies, the structural investigatiOn of biological macromolecules has become routine. In recent past, interaction of drug molecules with Oligonucleotides or polypeptides, DNA-protein interaction have revealed fine structural details that illustrate the substrate-receptor binding, drug recognition profile, and structural abnormalities of oligonucleotides, and underline their implications in the design of potent biodynamic agents. Individual structural studies on oligonucleotide sequences containing abasic sites have been published, but a detailed account decoding the contribution of flanking base pairs of an abasic site on the overall structure of a DNA has not been accomplished. It becomes essential to furnish such a study, which would decipher the role of flanking base pairs in a DNA containing a carcinogenic abasic site lesion. A complete 2D-NMR study generating structural parameters required for the structure refinement by molecular dynamics strategies would furnish such account, which will aid in designing more potent drugs in the treatment of cancers. A whole new approach has been developed recently by few research groups, by designing oligonucleotides covalently linked to a minor groove binding drug and estimating their hybridization capability with other DNA and RNA sequences. Such strongly binding DNA conjugates have a potential of antisense agents, which selectively bind to specific sequences, thus blocking their further replication/transcription in the management of cancer and AIDS. This approach is heralding a new horizon in handling the mutant DNA/RNA sequences, while dealing with nucleoproteins of AIDS virus or mutagenic cells. A DNA conjugate containing a CDPI3 moiety, and two isoteric guanine, ppG residues, has been designed and prepared by our collaborators at Epoch Pharmaceuticals, which will be evaluated by 2D-NMR methods for structural details. This study will help developing more potent antisense/antigene agents. A collaboration with Dr. Barry Schweitzer of Walt Disney Memorial Cancer Institute, Orlando, FL/Molecular Staging, Inc., New Haven, CT has been established, who will assist in various aspects of the proposal, specially in structure refinement protocols.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
2S06GM054650-04
Application #
6244916
Study Section
Minority Programs Review Committee (MPRC)
Project Start
1996-09-30
Project End
2003-09-29
Budget Start
Budget End
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Long Island University Brooklyn Campus
Department
Type
DUNS #
City
Brooklyn
State
NY
Country
United States
Zip Code
11548
Ratna, Warren N; Bhatt, Vrushank D; Chaudhary, Kawshik et al. (2016) Estrogen-responsive genes encoding egg yolk proteins vitellogenin and apolipoprotein II in chicken are differentially regulated by selective estrogen receptor modulators. Theriogenology 85:376-83
Cohen, Carl I; Ryu, Helen H (2015) A Longitudinal Study of the Outcome and Associated Factors of Subsyndromal and Syndromal Depression in Community-Dwelling Older Adults with Schizophrenia Spectrum Disorder. Am J Geriatr Psychiatry 23:925-33
Tuck, Natalie L; Consedine, Nathan S (2015) Breast cancer screening: the role of attachment. Psychol Health Med 20:400-9
Cohen, Carl I; Iqbal, Mudassar (2014) Longitudinal study of remission among older adults with schizophrenia spectrum disorder. Am J Geriatr Psychiatry 22:450-8
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Cohen, Carl I; Solanki, Dishal; Sodhi, Dimple (2013) Interpersonal conflict strategies and their impact on positive symptom remission in persons aged 55 and older with schizophrenia spectrum disorders. Int Psychogeriatr 25:47-53
Merz, Eva-Maria; Consedine, Nathan S (2012) Ethnic group moderates the association between attachment and well-being in later life. Cultur Divers Ethnic Minor Psychol 18:404-15
Consedine, Nathan S (2012) The demographic, system, and psychosocial origins of mammographic screening disparities: prediction of initiation versus maintenance screening among immigrant and non-immigrant women. J Immigr Minor Health 14:570-82
Consedine, Nathan S; Fiori, Katherine L; Magai, Carol (2012) Regulating emotion expression and regulating emotion experience: divergent associations with dimensions of attachment among older women. Attach Hum Dev 14:477-500

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