Martin

 

 

 

 

 

 

 


Bio:
B.S.: 1976 Caltech
Ph.D.: 1981 U.C. San Diego
Postdoc.: 1981-82 University of Gottingen, Germany
Postdoc.: 1983-85 SUNY Stony Brook, NY

Design of small-molecule CXCR4 antagonists for HIV and cancer treatment:

CXCR4 is a G-protein coupled receptor for the chemokine CXCL12 (SDF-1), which is involved in cell migration and proliferation. It is also a co-receptor used by the X4 strains of HIV, which predominate at later stages of infection, and is required for their entry into target cells. We are designing and synthesizing non-peptide small molecule inhibitors of CXCR4 based on modeling studies. Lead compounds that compete with known CXCR4 antagonists, such as the peptide T-140, are being investigated for their ability to inhibit HIV infection in vitro, and to inhibit tumor cell metastasis in vitro and in a mouse model.

Keywords: Biochemistry

Development of broad-spectrum antibacterial compounds:

Compounds with multiple biguanide groups such as chlorhexidine, alexidine, and PHMB are used as topical antimicrobials in a variety of settings. We have synthesized a series of small molecules with guanide, biguanide, and arylguanide functional groups that have comparable broad spectrum antibacterial activity, but lower cytotoxicity towards mammalian cells. We are investigating their mechanism of action and further optimizing their structures.

Keywords: Biochemistry

Recent Publications:

Wilkinson, R.A., Pincus, S.H., Song, K., Shepard, J.B., Weaver, A., Labib, M.E., and Teintze, M. (2013) Improved guanide compounds which bind the CXCR4 co-receptor and inhibit HIV infection. Bioorg. Med. Chem. Lett. 23:2197–2201. PMID: 23434419 PMCID: PMC3624624

Shepard, J.B., Wilkinson, R.A., Starkey, J.R. and Teintze, M. (2014) Novel Guanide Substituted Compounds bind to CXCR4 and Inhibit Breast Cancer Metastasis. Anti Cancer Drugs 25(1):8-16. doi: 10.1097. PMID: 24045366 PMCID: PMC3624624

Weaver, A.J., Shepard, J.B., Wilkinson, R.A., Watkins, R.L., Walton, S.K., Radke, A.R., Wright, T.J., Awel, M.B., Cooper, C., Erikson, E., Labib, M., Voyich, J.M. and Teintze, M. (2014) Antibacterial activity of THAM trisphenylguanide against Methicillin-resistant Staphylococcus aureus. PLoS One 9(5): e97742. doi:10.1371/journal.pone.00977

Pomwised, R., Intamaso, U., Teintze, M., Young, M.J. and Pincus, S.H. (2016) Coupling Peptide Antigens to Virus-Like Particles or to Protein Carriers Influences the Th1/Th2 Polarity of the Resulting Immune Response. Vaccines 4(2):15. DOI: 10.3390/vaccines4020015. PMID: 27164150

 Weaver, A.J., Peters, T.R., Tripet, B., van Vuren, A., Rakesh, Lee, R.E., Copie, V., and Teintze, M. (2018) Exposure of Methicillin-Resistant Staphylococcus aureus to Low Levels of the Antibacterial THAM-3ΦG Generates a Small Colony Drug-Resistant Phenotype. Sci. Rep. 8:9850.  DOI:10.1038/s41598-018-28283-3