Boston De Novo Design
Regine Bohacek, PhD
AlleGrow Modeling Software
Consulting and Modeling Services
Design with X-ray structures
Design with Pharmacophores
Design with "pseudo receptor"
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Bohacek R, Boosalis MS, McMartin C, Faller DV, Perrine SP.
Identification of novel small-molecule inducers of fetal hemoglobin using
pharmacophore and 'PSEUDO' receptor models.
Chem Biol Drug Des. 2006 May;67(5):318-28.

Azam M, Nardi V, Shakespeare WC, Metcalf CA 3rd, Bohacek RS, Wang Y,
Sundaramoorthi R, Sliz P, Veach DR, Bornmann WG, Clarkson B, Dalgarno DC, Sawyer
TK, Daley GQ.
Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase
dynamics in drug resistance.
Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9244-9. Epub 2006 Jun 5.

Dalgarno D, Stehle T, Narula S, Schelling P, van Schravendijk MR, Adams S,
Andrade L, Keats J, Ram M, Jin L, Grossman T, MacNeil I, Metcalf C 3rd,
Shakespeare W, Wang Y, Keenan T, Sundaramoorthi R, Bohacek R, Weigele M, Sawyer T.
Structural basis of Src tyrosine kinase inhibition with a new class of potent and
selective trisubstituted purine-based compounds.
Chem Biol Drug Des. 2006 Jan;67(1):46-57.

Sawyer TK, Shakespeare WC, Wang Y, Sundaramoorthi R, Huang WS, Metcalf CA
3rd, Thomas M, Lawrence BM, Rozamus L, Noehre J, Zhu X, Narula S, Bohacek RS,
Weigele M, Dalgarno DC.
Protein phosphorylation and signal transduction modulation: chemistry
perspectives for small-molecule drug discovery.
Med Chem. 2005 May;1(3):293-319. Review.

O'Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, Moseson EM, Rivera
VM, Tang H, Metcalf CA 3rd, Bohacek RS, Wang Y, Sundaramoorthi R, Shakespeare WC,
Dalgarno D, Clackson T, Sawyer TK, Deininger MW, Druker BJ.
Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based
oncogenic protein kinase inhibitor: implications for CML.
Blood. 2004 Oct 15;104(8):2532-9. Epub 2004 Jul 15.

Sawyer TK, Bohacek RS, Metcalf CA 3rd, Shakespeare WC, Wang Y, Sundaramoorthi
R, Keenan T, Narula S, Weigele M, Dalgarno DC.
Novel protein kinase inhibitors: SMART drug design technology.
Biotechniques. 2003 Jun;Suppl:2-10, 12-5. Review.

Sundaramoorthi R, Shakespeare WC, Keenan TP, Metcalf CA 3rd, Wang Y, Mani U,
Taylor M, Liu S, Bohacek RS, Narula SS, Dalgarno DC, van Schravandijk MR,
Violette SM, Liou S, Adams S, Ram MK, Keats JA, Weigle M, Sawyer TK, Weigele M.
Bone-targeted Src kinase inhibitors: novel pyrrolo- and pyrazolopyrimidine
Bioorg Med Chem Lett. 2003 Sep 15;13(18):3063-6. Erratum in: Bioorg Med Chem
Lett. 2003 Dec 15;13(24):4519.

Wang Y, Metcalf CA 3rd, Shakespeare WC, Sundaramoorthi R, Keenan TP, Bohacek
RS, van Schravendijk MR, Violette SM, Narula SS, Dalgarno DC, Haraldson C, Keats
J, Liou S, Mani U, Pradeepan S, Ram M, Adams S, Weigele M, Sawyer TK.
Bone-targeted 2,6,9-trisubstituted purines: novel inhibitors of Src tyrosine
kinase for the treatment of bone diseases.
Bioorg Med Chem Lett. 2003 Sep 15;13(18):3067-70.

Vu CB, Luke GP, Kawahata N, Shakespeare WC, Wang Y, Sundaramoorthi R, Metcalf
CA 3rd, Keenan TP, Pradeepan S, Corpuz E, Merry T, Bohacek RS, Dalgarno DC,
Narula SS, van Schravendijk MR, Ram MK, Adams S, Liou S, Keats JA, Violette SM,
Guan W, Weigele M, Sawyer TK.
Bone-targeted pyrido[2,3-d]pyrimidin-7-ones: potent inhibitors of Src tyrosine
kinase as novel antiresorptive agents.
Bioorg Med Chem Lett. 2003 Sep 15;13(18):3071-4.

Shakespeare WC, Metcalf CA 3rd, Wang Y, Sundaramoorthi R, Keenan T, Weigele
M, Bohacek RS, Dalgarno DC, Sawyer TK.
Novel bone-targeted Src tyrosine kinase inhibitor drug discovery.
Curr Opin Drug Discov Devel. 2003 Sep;6(5):729-41. Review.

Sundaramoorthi R, Kawahata N, Yang MG, Shakespeare WC, Metcalf CA 3rd, Wang
Y, Merry T, Eyermann CJ, Bohacek RS, Narula S, Dalgarno DC, Sawyer TK.
Structure-based design of novel nonpeptide inhibitors of the Src SH2
domain:phosphotyrosine mimetics exploiting multifunctional group replacement
Biopolymers. 2003;71(6):717-29.

Sawyer TK, Bohacek RS, Dalgarno DC, Eyermann CJ, Kawahata N, Metcalf CA 3rd,
Shakespeare WC, Sundaramoorthi R, Wang Y, Yang MG.
SRC homology-2 inhibitors: peptidomimetic and nonpeptide.
Mini Rev Med Chem. 2002 Oct;2(5):475-88. Review.

Bohacek RS, Dalgarno DC, Hatada M, Jacobsen VA, Lynch BA, Macek KJ, Merry T,
Metcalf CA 3rd, Narula SS, Sawyer TK, Shakespeare WC, Violette SM, Weigele M.
X-Ray structure of citrate bound to Src SH2 leads to a high-affinity,
bone-targeted Src SH2 inhibitor.
J Med Chem. 2001 Mar 1;44(5):660-3.

Ripka AS, Satyshur KA, Bohacek RS, Rich DH.
Aspartic protease inhibitors designed from computer-generated templates bind as
Org Lett. 2001 Jul 26;3(15):2309-12.

Dales NA, Bohacek RS, Satyshur KA, Rich DH.
Design and synthesis of unsymmetrical peptidyl urea inhibitors of aspartic
Org Lett. 2001 Jul 26;3(15):2313-6.

Greenspan PD, Clark KL, Tommasi RA, Cowen SD, McQuire LW, Farley DL, van
Duzer JH, Goldberg RL, Zhou H, Du Z, Fitt JJ, Coppa DE, Fang Z, Macchia W, Zhu L,
Capparelli MP, Goldstein R, Wigg AM, Doughty JR, Bohacek RS, Knap AK.
Identification of dipeptidyl nitriles as potent and selective inhibitors of
cathepsin B through structure-based drug design.
J Med Chem. 2001 Dec 20;44(26):4524-34.

Kawahata N, Yang MG, Luke GP, Shakespeare WC, Sundaramoorthi R, Wang Y,
Johnson D, Merry T, Violette S, Guan W, Bartlett C, Smith J, Hatada M, Lu X,
Dalgarno DC, Eyermann CJ, Bohacek RS, Sawyer TK.
A novel phosphotyrosine mimetic 4'-carboxymethyloxy-3'-phosphonophenylalanine
(Cpp): exploitation in the design of nonpeptide inhibitors of pp60(Src) SH2
Bioorg Med Chem Lett. 2001 Sep 3;11(17):2319-23.

Violette SM, Guan W, Bartlett C, Smith JA, Bardelay C, Antoine E, Rickles RJ,
Mandine E, van Schravendijk MR, Adams SE, Lynch BA, Shakespeare WC, Yang M,
Jacobsen VA, Takeuchi CS, Macek KJ, Bohacek RS, Dalgarno DC, Weigele M, Lesuisse
D, Sawyer TK, Baron R.
Bone-targeted Src SH2 inhibitors block Src cellular activity and
osteoclast-mediated resorption.
Bone. 2001 Jan;28(1):54-64.

Violette SM, Shakespeare WC, Bartlett C, Guan W, Smith JA, Rickles RJ,
Bohacek RS, Holt DA, Baron R, Sawyer TK.
A Src SH2 selective binding compound inhibits osteoclast-mediated resorption.
Chem Biol. 2000 Mar;7(3):225-35.

Metcalf CA 3rd, Eyermann CJ, Bohacek RS, Haraldson CA, Varkhedkar VM, Lynch
BA, Bartlett C, Violette SM, Sawyer TK.
Structure-based design and solid-phase parallel synthesis of phosphorylated
nonpeptides to explore hydrophobic binding at the Src SH2 domain.
J Comb Chem. 2000 Jul-Aug;2(4):305-13.

Shakespeare W, Yang M, Bohacek R, Cerasoli F, Stebbins K, Sundaramoorthi R,
Azimioara M, Vu C, Pradeepan S, Metcalf C 3rd, Haraldson C, Merry T, Dalgarno D,
Narula S, Hatada M, Lu X, van Schravendijk MR, Adams S, Violette S, Smith J, Guan
W, Bartlett C, Herson J, Iuliucci J, Weigele M, Sawyer T.
Structure-based design of an osteoclast-selective, nonpeptide src homology 2
inhibitor with in vivo antiresorptive activity.
Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9373-8.

Shakespeare WC, Bohacek RS, Azimioara MD, Macek KJ, Luke GP, Dalgarno DC,
Hatada MH, Lu X, Violette SM, Bartlett C, Sawyer TK.
Structure-based design of novel bicyclic nonpeptide inhibitors for the src SH2
J Med Chem. 2000 Oct 19;43(21):3815-9. No abstract available.

Buchanan JL, Bohacek RS, Luke GP, Hatada M, Lu X, Dalgarno DC, Narula SS,
Yuan R, Holt DA.
Structure-based design and synthesis of a novel class of Src SH2 inhibitors.
Bioorg Med Chem Lett. 1999 Aug 16;9(16):2353-8.

Vu CB, Corpuz EG, Merry TJ, Pradeepan SG, Bartlett C, Bohacek RS, Botfield
MC, Eyermann CJ, Lynch BA, MacNeil IA, Ram MK, van Schravendijk MR, Violette S,
Sawyer TK.
Discovery of potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70.
J Med Chem. 1999 Oct 7;42(20):4088-98.

Shakespeare WC, Bohacek RS, Narula SS, Azimioara MD, Yuan RW, Dalgarno DC,
Madden L, Botfield MC, Holt DA.
An efficient synthesis of a 4'-phosphonodifluoromethyl-3'-formyl-phenylalanine
containing SRC SH2 ligand.
Bioorg Med Chem Lett. 1999 Nov 1;9(21):3109-12.

Ripka AS, Bohacek RS, Rich DH.
Synthesis of novel cyclic protease inhibitors using Grubbs olefin metathesis.
Bioorg Med Chem Lett. 1998 Feb 17;8(4):357-60.

Ksander GM, de Jesus R, Yuan A, Ghai RD, Trapani A, McMartin C, Bohacek R.
Ortho-substituted benzofused macrocyclic lactams as zinc metalloprotease
J Med Chem. 1997 Feb 14;40(4):495-505.

Ksander GM, de Jesus R, Yuan A, Ghai RD, McMartin C, Bohacek R.
Meta-substituted benzofused macrocyclic lactams as zinc metalloprotease
J Med Chem. 1997 Feb 14;40(4):506-14.

McMartin C, Bohacek RS.
QXP: powerful, rapid computer algorithms for structure-based drug design.
J Comput Aided Mol Des. 1997 Jul;11(4):333-44.

Bohacek RS, McMartin C.
Modern computational chemistry and drug discovery: structure generating programs.
Curr Opin Chem Biol. 1997 Aug;1(2):157-61. Review.

Bohacek RS, McMartin C, Guida WC.
The art and practice of structure-based drug design: a molecular modeling
Med Res Rev. 1996 Jan;16(1):3-50. Review.

McMartin C, Bohacek RS.
Flexible matching of test ligands to a 3D pharmacophore using a molecular
superposition force field: comparison of predicted and experimental conformations
of inhibitors of three enzymes.
J Comput Aided Mol Des. 1995 Jun;9(3):237-50.

6: Bohacek RS, McMartin C.
Exploring the universe of molecules for new drugs.
Nat Med. 1995 Feb;1(2):177-8.

7: Taralp A, Kaplan H, Sytwu II, Vlattas I, Bohacek R, Knap AK, Hirama T, Huber
CP, Hasnain S.
Characterization of the S3 subsite specificity of cathepsin B.
J Biol Chem. 1995 Jul 28;270(30):18036-43.

8: Gonnella NC, Bohacek R, Zhang X, Kolossváry I, Paris CG, Melton R, Winter C,
Hu SI, Ganu V.
Bioactive conformation of stromelysin inhibitors determined by transferred
nuclear Overhauser effects.
Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):462-6.

Gonnella NC, Zhang X, Jin Y, Prakash O, Paris CG, Kolossváry I, Guida WC,
Bohacek RS, Vlattas I, Sytwu T.
Solvent effects on the conformation of cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu-). An NMR
spectroscopy and molecular modeling study.
Int J Pept Protein Res. 1994 May;43(5):454-62.

MacPherson LJ, Bayburt EK, Capparelli MP, Bohacek RS, Clarke FH, Ghai RD,
Sakane Y, Berry CJ, Peppard JV, Trapani AJ.
Design and synthesis of an orally active macrocyclic neutral endopeptidase 24.11
J Med Chem. 1993 Nov 26;36(24):3821-8.

Bohacek RS, McMartin C.
Definition and display of steric, hydrophobic, and hydrogen-bonding properties of
ligand binding sites in proteins using Lee and Richards accessible surface:
validation of a high-resolution graphical tool for drug design.
J Med Chem. 1992 May 15;35(10):1671-84.

Bohacek RS, Guida WC.
A rapid method for the computation, comparison and display of molecular volumes.
J Mol Graph. 1989 Jun;7(2):113-7.

Roberts DC, Bohacek RS.
Estimation of peptide hormone noncovalent binding site functionality from
frequencies of interaction of amino acid side chains in proteins.
Int J Pept Protein Res. 1983 May;21(5):491-512.

Bohacek RS, Davison B, Roberts DC.
Application of pattern recognition techniques to the analysis of protein crystal
structure data. I. Characteristics of per-residue side chain contact frequency
Int J Pept Protein Res. 1983 Jul;22(1):21-31.