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Barry M. Goldstein, M.D., Ph.D.

Barry M. Goldstein, M.D., Ph.D.

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About Me

Faculty Appointments

Associate Professor - Department of Biochemistry and Biophysics (SMD)

Credentials

Education

PhD | Univ Rochester Sch Med/Dent. Biophysics. 1982

MD | Univ Rochester Sch Med/Dent. Medicine. 1981

MS | Univ Rochester Sch Med/Dent. Biophysics. 1976

BS | Union College. Physics. 1973

Research

The structure of a biologically active molecule (i.e. a drug) is intimately related to its function. Our laboratory employs the technique of macromolecular crystallography to elucidate molecular structure, and to relate this structure to biological function. Crystallographic methods are used to defi...
The structure of a biologically active molecule (i.e. a drug) is intimately related to its function. Our laboratory employs the technique of macromolecular crystallography to elucidate molecular structure, and to relate this structure to biological function. Crystallographic methods are used to define the structures of complexes between active ligands and their enzymatic targets. This information is used in conjunction with ancillary modeling and computational techniques to identify, at the molecular level, specific interactions important in stabilizing these complexes.

Current research projects examine a series of chemotherapeutic dinucleotide analogues of the cofactor NAD. These agents act as general inhibitors of the class of enzymes known as dehydrogenases. Different inhibitors show marked variations in specificities and affinities for different enzymes. These variations in ligand binding can be attributed to distinct alterations in both intra- and intermolecular interactions observed in the enzyme-inhibitor complexes.

Structural results at atomic resolution are correlated with biochemical and pharmacological data. The ultimate aim of these studies is to identify conformational features which enhance drug activity. These features can then be preserved in the intelligent design of new analogues.

Publications

Journal Articles

Overcoming lower-extremity wound defects using hydrocolloid framing.

Goldstein BM

Advances in skin & wound care.. 2011 May 24 (5):221-4. Epub 1900 01 01.

Demystifying electrosurge.

Goldstein BM

Dentistry today.. 2005 November 24 (11):114-6, 118, 120. Epub 1900 01 01.

Coupling of MBP fusion protein cleavage with sparse matrix crystallization screens to overcome problematic protein solubility.

Gruswitz F, Frishman M, Goldstein BM, Wedekind JE

BioTechniques.. 2005 October 39 (4):476, 478, 480. Epub 1900 01 01.

Localization of a pH-dependent, A2 subunit-interactive surface within the factor VIIIa A1 subunit.

Nogami K, Wakabayashi H, Ansong C, Fay PJ

Biochimica et biophysica acta.. 2004 September 11701 (1-2):25-35. Epub 1900 01 01.

Crystal structure and amide H/D exchange of binary complexes of alcohol dehydrogenase from Bacillus stearothermophilus: insight into thermostability and cofactor binding.

Ceccarelli C, Liang ZX, Strickler M, Prehna G, Goldstein BM, Klinman JP, Bahnson BJ

Biochemistry.. 2004 May 1143 (18):5266-77. Epub 1900 01 01.

Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic target.

Pankiewicz KW, Patterson SE, Black PL, Jayaram HN, Risal D, Goldstein BM, Stuyver LJ, Schinazi RF

Current medicinal chemistry.. 2004 April 11 (7):887-900. Epub 1900 01 01.

Crystallographic studies on the complex behavior of nicotine binding to P450cam (CYP101).

Strickler M, Goldstein BM, Maxfield K, Shireman L, Kim G, Matteson DS, Jones JP

Biochemistry.. 2003 October 2142 (41):11943-50. Epub 1900 01 01.

The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C-nucleosides related to nicotinamide riboside.

Pankiewicz KW, Watanabe KA, Lesiak-Watanabe K, Goldstein BM, Jayaram HN

Current medicinal chemistry.. 2002 April 9 (7):733-41. Epub 1900 01 01.

Active site mutations of cytochrome p450cam alter the binding, coupling, and oxidation of the foreign substrates (R)- and (s)-2-ethylhexanol.

French KJ, Rock DA, Rock DA, Manchester JI, Goldstein BM, Jones JP

Archives of biochemistry and biophysics.. 2002 February 15398 (2):188-97. Epub 1900 01 01.

Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia.

Pankiewicz KW, Lesiak-Watanabe KB, Watanabe KA, Patterson SE, Jayaram HN, Yalowitz JA, Miller MD, Seidman M, Majumdar A, Prehna G, Goldstein BM

Journal of medicinal chemistry.. 2002 January 3145 (3):703-12. Epub 1900 01 01.

Benign synthesis of 2-ethylhexanoic acid by cytochrome P450cam: enzymatic, crystallographic, and theoretical studies.

French KJ, Strickler MD, Rock DA, Rock DA, Bennett GA, Wahlstrom JL, Goldstein BM, Jones JP

Biochemistry.. 2001 August 1440 (32):9532-8. Epub 1900 01 01.

A new C-nucleoside analogue of tiazofurin: synthesis and biological evaluation of 2-beta-D-ribofuranosylimidazole-4-carboxamide (imidazofurin).

Franchetti P, Marchetti S, Cappellacci L, Yalowitz JA, Jayaram HN, Goldstein BM, Grifantini M

Bioorganic & medicinal chemistry letters.. 2001 January 811 (1):67-9. Epub 1900 01 01.

Synthesis, conformational analysis, and biological activity of C-thioribonucleosides related to tiazofurin.

Franchetti P, Marchetti S, Cappellacci L, Jayaram HN, Yalowitz JA, Goldstein BM, Barascut JL, Dukhan D, Imbach JL, Grifantini M

Journal of medicinal chemistry.. 2000 April 643 (7):1264-70. Epub 1900 01 01.

Conformational constraints in NAD analogs: implications for dehydrogenase binding and specificity.

Goldstein BM, Colby TD

Advances in enzyme regulation.. 2000 40 :405-26. Epub 1900 01 01.

IMP dehydrogenase : structural aspects of inhibitor binding.

Goldstein BM, Colby TD

Current medicinal chemistry.. 1999 July 6 (7):519-36. Epub 1900 01 01.

Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design.

Colby TD, Vanderveen K, Strickler MD, Markham GD, Goldstein BM

Proceedings of the National Academy of Sciences of the United States of America.. 1999 March 3096 (7):3531-6. Epub 1900 01 01.

Active site modifications in a double mutant of liver alcohol dehydrogenase: structural studies of two enzyme-ligand complexes.

Colby TD, Bahnson BJ, Chin JK, Klinman JP, Goldstein BM

Biochemistry.. 1998 June 3037 (26):9295-304. Epub 1900 01 01.

Synthesis of a methylenebis(phosphonate) analogue of mycophenolic adenine dinucleotide: a glucuronidation-resistant MAD analogue of NAD.

Lesiak K, Watanabe KA, Majumdar A, Powell J, Seidman M, Vanderveen K, Goldstein BM, Pankiewicz KW

Journal of medicinal chemistry.. 1998 February 1241 (4):618-22. Epub 1900 01 01.

A link between protein structure and enzyme catalyzed hydrogen tunneling.

Bahnson BJ, Colby TD, Chin JK, Goldstein BM, Klinman JP

Proceedings of the National Academy of Sciences of the United States of America.. 1997 November 2594 (24):12797-802. Epub 1900 01 01.

Synthesis of nonhydrolyzable analogues of thiazole-4-carboxamide and benzamide adenine dinucleotide containing fluorine atom at the C2' of adenine nucleoside: induction of K562 differentiation and inosine monophosphate dehydrogenase inhibitory activity.

Lesiak K, Watanabe KA, Majumdar A, Seidman M, Vanderveen K, Goldstein BM, Pankiewicz KW

Journal of medicinal chemistry.. 1997 August 140 (16):2533-8. Epub 1900 01 01.

Synthesis, structure, and antiproliferative activity of selenophenfurin, an inosine 5'-monophosphate dehydrogenase inhibitor analogue of selenazofurin.

Franchetti P, Cappellacci L, Sheikha GA, Jayaram HN, Gurudutt VV, Sint T, Schneider BP, Jones WD, Goldstein BM, Perra G, De Montis A, Loi AG, La Colla P, Grifantini M

Journal of medicinal chemistry.. 1997 May 2340 (11):1731-7. Epub 1900 01 01.

The practical synthesis of a methylenebisphosphonate analogue of benzamide adenine dinucleotide: inhibition of human inosine monophosphate dehydrogenase (type I and II).

Pankiewicz KW, Lesiak K, Zatorski A, Goldstein BM, Carr SF, Sochacki M, Majumdar A, Seidman M, Watanabe KA

Journal of medicinal chemistry.. 1997 April 1140 (8):1287-91. Epub 1900 01 01.

Chemical synthesis of benzamide adenine dinucleotide: inhibition of inosine monophosphate dehydrogenase (types I and II).

Zatorski A, Watanabe KA, Carr SF, Goldstein BM, Pankiewicz KW

Journal of medicinal chemistry.. 1996 June 739 (12):2422-6. Epub 1900 01 01.

Furanfurin and thiophenfurin: two novel tiazofurin analogues. Synthesis, structure, antitumor activity, and interactions with inosine monophosphate dehydrogenase.

Franchetti P, Cappellacci L, Grifantini M, Barzi A, Nocentini G, Yang H, O'Connor A, Jayaram HN, Carrell C, Goldstein BM

Journal of medicinal chemistry.. 1995 September 1538 (19):3829-37. Epub 1900 01 01.

Potent inhibitors of human inosine monophosphate dehydrogenase type II. Fluorine-substituted analogues of thiazole-4-carboxamide adenine dinucleotide.

Zatorski A, Goldstein BM, Colby TD, Jones JP, Pankiewicz KW

Journal of medicinal chemistry.. 1995 March 3138 (7):1098-105. Epub 1900 01 01.

Synthesis, Antitumor Activity and Crystallographic Studies of Analogues of Tiazofurin

Cappellacci, L.; Franchetti, P.; Grifantini, M.; Messini, L.; Abu Sheikha, G.; Nocenti, G.; Moraca, R.; Goldstein, B.M.;.

Nucleosides and Nucleotides. 1995; 14(3): 637-640.

Crystallographic studies of isosteric NAD analogues bound to alcohol dehydrogenase: specificity and substrate binding in two ternary complexes.

Li H, Hallows WH, Punzi JS, Pankiewicz KW, Watanabe KA, Goldstein BM

Biochemistry.. 1994 October 433 (39):11734-44. Epub 1900 01 01.

C-glycosyl bond conformation in oxazofurin: crystallographic and computational studies of the oxazole analogue of tiazofurin.

Goldstein BM, Li H, Hallows WH, Langs DA, Franchetti P, Cappellacci L, Grifantini M

Journal of medicinal chemistry.. 1994 May 2737 (11):1684-8. Epub 1900 01 01.

CNAD: a potent and specific inhibitor of alcohol dehydrogenase.

Goldstein BM, Li H, Jones JP, Bell JE, Zeidler J, Pankiewicz KW, Watanabe KA

Journal of medicinal chemistry.. 1994 February 437 (3):392-9. Epub 1900 01 01.

Crystallographic studies of two alcohol dehydrogenase-bound analogues of thiazole-4-carboxamide adenine dinucleotide (TAD), the active anabolite of the antitumor agent tiazofurin.

Li H, Hallows WH, Punzi JS, Marquez VE, Carrell HL, Pankiewicz KW, Watanabe KA, Goldstein BM

Biochemistry.. 1994 January 1133 (1):23-32. Epub 1900 01 01.

Synthesis of thiazole-4-carboxamide-adenine difluoromethylenediphosphonates substituted with fluorine at C-2' of the adenosine.

Zatorski A, Lipka P, Mollova N, Schram KH, Goldstein BM, Watanabe KA, Pankiewicz KW

Carbohydrate research.. 1993 October 18249 (1):95-108. Epub 1900 01 01.

Solid-state and solution conformations of isotiazofurin: crystallographic, computational and 1H NMR studies.

Li H, Kennedy SD, Goldstein BM

Acta crystallographica. Section B, Structural science. 1993 August 149 ( Pt 4) :729-38. Epub 1900 01 01.

A database study of nonbonded intramolecular sulfur-nucleophile contacts.

Burling FT, Goldstein BM

Acta crystallographica. Section B, Structural science. 1993 August 149 ( Pt 4) :738-44. Epub 1900 01 01.

Synthesis of isosteric analogues of nicotinamide adenine dinucleotide containing C-nucleotide of nicotinamide or picolinamide.

Pankiewicz KW, Zeidler J, Ciszewski LA, Bell JE, Goldstein BM, Jayaram HN, Watanabe KA

Journal of medicinal chemistry.. 1993 June 2536 (13):1855-9. Epub 1900 01 01.

Synthesis of Carbocyclic Analogues of 1-beta-D-Psicoofuranosyl Nucleosides. Psico-cyclopentenyladenosine (Psicoplanocin A) and Psico-cyclopentenylcytosine

Bodenteich, M.; Marquez; Barchi, J.J. Jr.; Hallows, W.H.; Goldstein, B.M.; Driscoll, J.S.;.

J. Org. Chem. 1993; 58(3): 6009-6015.

Structures of the 4-cyano and 4-methylamidate analogs of tiazofurin.

Burling FT, Hallows WH, Phelan MJ, Gabrielsen B, Goldstein BM

Acta crystallographica. Section B, Structural science. 1992 October 148 ( Pt 5) :677-83. Epub 1900 01 01.

Carboxamide group conformation in the nicotinamide and thiazole-4-carboxamide rings: implications for enzyme binding.

Li H, Goldstein BM

Journal of medicinal chemistry.. 1992 September 1835 (19):3560-7. Epub 1900 01 01.

Computational Studies of Nonbonded Sulfur-Oxygen and Selenium-Oxygen Interactions in the Thiazole and Selenazole Nucleosides

Burling, F.T.; Goldstein, B.M.;.

J. Am. Chem. Soc. 1992; 114(3): 2313-2320.

Synthesis and Structural characterization of (±) Neplanocin F

Bodenteich, M.; Marquez, V.E.; Hallows, W.H.; Goldstein, B.M.;.

J. Org. Chem. 1992; 57(3): 2071-2076.

Relationship of cardiac hemodynamic and biochemical adaptations to mortality during long-term aortic constriction.

Crandall DL, Goldstein BM, Ferraro GD, Cervoni P

Proceedings of the Society for Experimental Biology and Medicine.. 1991 November 198 (2):747-53. Epub 1900 01 01.

Cytotoxicity of tiazofurin and its arabinose and xylose analogues in K562 cells.

Zhen W, Jayaram HN, Marquez VE, Goldstein BM, Cooney DA, Weber G

Biochemical and biophysical research communications.. 1991 October 31180 (2):933-8. Epub 1900 01 01.

Induction of HL60 cell differentiation by tiazofurin and its analogues: characterization and efficacy.

Goldstein BM, Leary JF, Farley BA, Marquez VE, Levy PC, Rowley PT

Blood.. 1991 August 178 (3):593-8. Epub 1900 01 01.

Structures of the 2',3'-dideoxy and 2',3'-didehydro-2',3'-dideoxy analogs of tiazofurin.

Burling FT, Gabrielsen B, Goldstein BM

Acta crystallographica. Section C, Crystal structure communications.. 1991 June 1547 ( Pt 6) :1272-5. Epub 1900 01 01.

Myocardial Imaging Agents: Synthesis, Characterization and Evaluation of [(Z) and (Z,E)-(1-[82Br]Bromo-1-penten-5-yl)] triphenylphosphonium Cations

Srivastava,P.C.; Knapp, F.F. Jr.; Callahan, A.P.; Goldstein, B.M.;.

J. Labeled Comp. and Radiopharm. 1991; 28(3): 1161-1169.

Dehydrogenase binding by tiazofurin anabolites.

Goldstein BM, Bell JE, Marquez VE

Journal of medicinal chemistry.. 1990 April 33 (4):1123-7. Epub 1900 01 01.

77Se NMR and Crystallographic Studies of Selenazofurin and its 5-amino Derivative

Goldstein, B.M.; Kennedy, S.D.; Hennen, W.J. ;.

J. Am. Chem. 1990; : 8265-8268.

The effect of chlorpheniramine on asthma.

Ricci AR, Settipane RJ, Goldstein BM, Kalliel JN, Settipane GA

Allergy proceedings : the official journal of regional and state

High frequency of atopic asthma in a pulmonary clinic population.

Kalliel JN, Goldstein BM, Braman SS, Settipane GA

Chest.. 1989 December 96 (6):1336-40. Epub 1900 01 01.

Synthesis of 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activities.

Tseng CK, Marquez VE, Fuller RW, Goldstein BM, Haines DR, McPherson H, Parsons JL, Shannon WM, Arnett G, Hollingshead M

Journal of medicinal chemistry.. 1989 July 32 (7):1442-6. Epub 1900 01 01.

Effect of varying concentrations of linoleic acid on alpha-adrenoceptor responses in spontaneously hypertensive rats.

Crandall DL, Goldstein BM, Lozito RJ, Lizzo FH, Cervoni P

Prostaglandins, leukotrienes, and essential fatty acids.. 1988 August 33 (2):115-9. Epub 1900 01 01.

Ara-tiazofurin: conservation of structural features in an unusual thiazole nucleoside.

Goldstein BM, Mao DT, Marquez VE

Journal of medicinal chemistry.. 1988 May 31 (5):1026-31. Epub 1900 01 01.

Development of an animal model for investigating disparate myocardial effects of obesity and hypertension.

Crandall DL, Goldstein BM, Lizzo FH, Lozito RJ, Cervoni P

Journal of applied physiology.. 1988 March 64 (3):1094-7. Epub 1900 01 01.

Introduction to the Crystallographic Literature: A Course for the Non-specialist

Goldstein, B.M.;.

J. Chem. Ed. 1988; 65(3): 508-512.

A transfer nuclear Overhauser effect study of coenzyme binding to distinct sites in binary and ternary complexes in glutamate dehydrogenase.

Banerjee A, Levy HR, Levy GC, LiMuti C, Goldstein BM, Bell JE

Biochemistry.. 1987 December 1526 (25):8443-50. Epub 1900 01 01.

Myocardial adaptations to dietary sucrose in spontaneously hypertensive rats.

Crandall DL, Goldstein BM, Lizzo FH, Lozito RJ, Cervoni P

Research communications in chemical pathology and

Hemodynamics of obesity: influence of pattern of adipose tissue cellularity.

Crandall DL, Goldstein BM, Lizzo FH, Gabel RA, Cervoni P

The American journal of physiology.. 1986 August 251 (2 Pt 2):R314-9. Epub 1900 01 01.

Analogues of platelet activating factor. 5. Multiple oxygen substitution of the alkoxy chain.

Wissner A, Kohler CA, Goldstein BM

Journal of medicinal chemistry.. 1986 July 29 (7):1315-9. Epub 1900 01 01.

Analogues of platelet activating factor. 4. Some modifications of the phosphocholine moiety.

Wissner A, Schaub RE, Sum PE, Kohler CA, Goldstein BM

Journal of medicinal chemistry.. 1986 March 29 (3):328-33. Epub 1900 01 01.

Cis/trans Disorder in (5-Bromo-4-Pentenyl) triphenylphosphonium Iodide

Goldstein, B.M.; Takusagawa, F.; Srivastava, P.C.; Knapp, F.;.

Acta Cryst. 1986; C42(3): 570-573.

Crystal and Molecular Structure of a Chiral-Specific DNA Binding Agent: tris(4,7-diphenylphenanthroline) ruthenium (II)

Goldstein, B.M.; Barton, J.; Berman, H.M.;.

J. Inorg. Chem. 1986; 25(3): 842-847.

Analogues of platelet activating factor (PAF). 2. Some modifications of the glycerine backbone.

Wissner A, Schaub RE, Sum PE, Kohler CA, Goldstein BM

Journal of medicinal chemistry.. 1985 September 28 (9):1181-7. Epub 1900 01 01.

Analogues of platelet activating factor. 3. Replacement of the phosphate moiety with a sulfonylbismethylene group.

Wissner A, Kohler CA, Goldstein BM

Journal of medicinal chemistry.. 1985 September 28 (9):1365-7. Epub 1900 01 01.

Structural Studies of a New Antitumor and Antiviral Agent:

Goldstein, B.M.; Takusagawa, F.; Berman, H.M.; Srivastava, P.C.; Robins, R.K.;.

J. Am. Chem. Soc. 1985; 107(3): 1394-1400.

Effects of the antihypertensive prostaglandin analog CL 115,347 on cardiac output distribution in the spontaneously hypertensive rat.

Crandall DL, Goldstein BM, Gabel R, Lizzo FH, Cervoni P

Journal of cardiovascular pharmacology.. 1985 7 (5):996-1002. Epub 1900 01 01.

Evidence for the lack of interaction between (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine and alpha-adrenoceptors in vivo and in vitro.

Cervoni P, Goldstein BM, Herzlinger H, Lai FM, Quirk GJ

British journal of pharmacology.. 1984 October 83 (2):511-7. Epub 1900 01 01.

Effect of platelet activating factor (PAF) on blood flow distribution in the spontaneously hypertensive rat.

Goldstein BM, Gabel RA, Huggins FJ, Cervoni P, Crandall DL

Life sciences.. 1984 September 2435 (13):1373-8. Epub 1900 01 01.

Analogues of platelet activating factor (PAF). 1. Some modifications of the alkoxy chain.

Wissner A, Sum PE, Schaub RE, Kohler CA, Goldstein BM

Journal of medicinal chemistry.. 1984 September 27 (9):1174-81. Epub 1900 01 01.

Hemodynamic effects of weight reduction in the obese rat.

Crandall DL, Goldstein BM, Gabel RA, Cervoni P

The American journal of physiology.. 1984 August 247 (2 Pt 2):R266-71. Epub 1900 01 01.

Adipocyte blood flow: influence of age, anatomic location, and dietary manipulation.

Crandall DL, Goldstein BM, Huggins F, Cervoni P

The American journal of physiology.. 1984 July 247 (1 Pt 2):R46-51. Epub 1900 01 01.

Physiologic determinants of primary impressions for complete dentures.

Klein IE, Goldstein BM

The Journal of prosthetic dentistry.. 1984 May 51 (5):611-6. Epub 1900 01 01.

Crystallization and preliminary X-ray study of a complex between d(ATGCAT) and actinomycin D.

Takusagawa F, Goldstein BM, Youngster S, Jones RA, Berman HM

The Journal of biological chemistry.. 1984 April 25259 (8):4714-5. Epub 1900 01 01.

Structural Studies of a New Antitumor Agent: Tiazofurin and its Inactive Analogues

Goldstein, B.M.; Takusagawa, F.; Berman, H.M.; Srivastava, P.C.; Robins, R.K.;.

J. Am. Chem. Soc. 1983; 105(3): 7416-7422.

Disposition of catecholamines in cardiovascular tissues of aorta coarcted hypertensive rats.

Goldstein BM, Lai FM, Herzlinger H, Cervoni P

Life sciences.. 1982 October 1131 (15):1633-8. Epub 1900 01 01.

Submucosal root retention. A two-year clinical observation.

MacEntee MI, Goldstein BM, Price C

The Journal of prosthetic dentistry.. 1982 May 47 (5):483-7. Epub 1900 01 01.

Disorder in the Structure of Trisodium Phosphorothioate Dodecahydrate

Goldstein, B.M.;.

Acta. Cryst. 1982; B38(3): 1116-1120.

Modulation of the baroreceptor reflex by central administration of angiotensin.

Goldstein BM, Heitz DC, Shaffer RA, Brody MJ

European journal of pharmacology.. 1974 May 26 (2):212-9. Epub 1900 01 01.

Metastable and Equilibrium Phases in Dilute V&endash;N Alloys

Potter, D.I.; Epstein, H.D.; Goldstein, B.M.;.

Metallurgical Transactions. 1974; 5(3): 2075-2082.