Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum

Komagal Kannan Sivaraman; Alessandro Paiardini; Marcin Sienczyk; Chiara Ruggeri; Christine Oellig; John P Dalton; Peter John Scammells; Marcin Drag; Sheena McGowan

doi:10.1021/jm4005972

Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum

Komagal Kannan Sivaraman, Alessandro Paiardini, Marcin Sienczyk, Chiara Ruggeri, Christine Oellig, John P Dalton, Peter John Scammells, Marcin Drag, Sheena McGowan

Research output: Contribution to journal › Article › Research › peer-review

42 Citations (Scopus)

Abstract

The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.

Original language	English
Pages (from-to)	5213 - 5217
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	56
Issue number	12
DOIs	https://doi.org/10.1021/jm4005972
Publication status	Published - 2013

Access to Document

10.1021/jm4005972

RM sElocation

Cite this

Kannan Sivaraman, K., Paiardini, A., Sienczyk, M., Ruggeri, C., Oellig, C., Dalton, J. P., Scammells, P. J., Drag, M., & McGowan, S. (2013). Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum. Journal of Medicinal Chemistry, 56(12), 5213 - 5217. https://doi.org/10.1021/jm4005972

Kannan Sivaraman, Komagal ; Paiardini, Alessandro ; Sienczyk, Marcin ; Ruggeri, Chiara ; Oellig, Christine ; Dalton, John P ; Scammells, Peter John ; Drag, Marcin ; McGowan, Sheena. / Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 12. pp. 5213 - 5217.

@article{b4d50358b91c486190cf4c3916fad97a,

title = "Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum",

abstract = "The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.",

author = "{Kannan Sivaraman}, Komagal and Alessandro Paiardini and Marcin Sienczyk and Chiara Ruggeri and Christine Oellig and Dalton, {John P} and Scammells, {Peter John} and Marcin Drag and Sheena McGowan",

year = "2013",

doi = "10.1021/jm4005972",

language = "English",

volume = "56",

pages = "5213 -- 5217",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "12",

}

Kannan Sivaraman, K, Paiardini, A, Sienczyk, M, Ruggeri, C, Oellig, C, Dalton, JP, Scammells, PJ, Drag, M & McGowan, S 2013, 'Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum', Journal of Medicinal Chemistry, vol. 56, no. 12, pp. 5213 - 5217. https://doi.org/10.1021/jm4005972

Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum. / Kannan Sivaraman, Komagal; Paiardini, Alessandro; Sienczyk, Marcin; Ruggeri, Chiara; Oellig, Christine; Dalton, John P; Scammells, Peter John; Drag, Marcin; McGowan, Sheena.

In: Journal of Medicinal Chemistry, Vol. 56, No. 12, 2013, p. 5213 - 5217.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum

AU - Kannan Sivaraman, Komagal

AU - Paiardini, Alessandro

AU - Sienczyk, Marcin

AU - Ruggeri, Chiara

AU - Oellig, Christine

AU - Dalton, John P

AU - Scammells, Peter John

AU - Drag, Marcin

AU - McGowan, Sheena

PY - 2013

Y1 - 2013

N2 - The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.

AB - The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.

UR - http://pubs.acs.org/doi/pdf/10.1021/jm4005972

U2 - 10.1021/jm4005972

DO - 10.1021/jm4005972

M3 - Article

VL - 56

SP - 5213

EP - 5217

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 12

ER -