Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics

Michael H Gelb; Wesley C Van Voorhis; Frederick S Buckner; Kohei Yokoyama; Richard Eastman; Elisabeth P Carpenter; Chrysoula Panethymitaki; Katherine A Brown; Deborah F Smith

Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics

Michael H Gelb, Wesley C Van Voorhis, Frederick S Buckner, Kohei Yokoyama, Richard Eastman, Elisabeth P Carpenter, Chrysoula Panethymitaki, Katherine A Brown, Deborah F Smith

Vice Chancellor's Office

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

Abstract

To accelerate progress in the development of therapeutics for protozoan parasitic diseases, we are studying enzymes active in co- and post-translational protein modification that are already the focus of drug development in other eukaryotic systems. Inhibitors of the protein farnesyltransferases (PFT) are well-established antitumour agents of low cytotoxicity and known pharmokinetic properties, while inhibitors of N-myristoyl transferase show both selectivity and specificity in the treatment of fungal infections. Here, we summarise the current evidence that supports the targeting of these ubiquitous eukaryotic enzymes for drug development against trypanosomatid infections and malaria.

Original language	English
Pages (from-to)	155-63
Number of pages	9
Journal	MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume	126
Issue number	2
Publication status	Published - Feb 2003

Bibliographical note

Keywords

Acyltransferases
Alkyl and Aryl Transferases
Animals
Antimalarials
Chemistry, Pharmaceutical
Drug Design
Plasmodium
Protein Conformation
Trypanocidal Agents
Trypanosoma

Cite this

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title = "Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics",

abstract = "To accelerate progress in the development of therapeutics for protozoan parasitic diseases, we are studying enzymes active in co- and post-translational protein modification that are already the focus of drug development in other eukaryotic systems. Inhibitors of the protein farnesyltransferases (PFT) are well-established antitumour agents of low cytotoxicity and known pharmokinetic properties, while inhibitors of N-myristoyl transferase show both selectivity and specificity in the treatment of fungal infections. Here, we summarise the current evidence that supports the targeting of these ubiquitous eukaryotic enzymes for drug development against trypanosomatid infections and malaria.",

keywords = "Acyltransferases, Alkyl and Aryl Transferases, Animals, Antimalarials, Chemistry, Pharmaceutical, Drug Design, Plasmodium, Protein Conformation, Trypanocidal Agents, Trypanosoma",

author = "Gelb, {Michael H} and {Van Voorhis}, {Wesley C} and Buckner, {Frederick S} and Kohei Yokoyama and Richard Eastman and Carpenter, {Elisabeth P} and Chrysoula Panethymitaki and Brown, {Katherine A} and Smith, {Deborah F}",

year = "2003",

month = feb,

language = "English",

volume = "126",

pages = "155--63",

journal = "MOLECULAR AND BIOCHEMICAL PARASITOLOGY",

issn = "0166-6851",

publisher = "Elsevier",

number = "2",

}

Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics. / Gelb, Michael H; Van Voorhis, Wesley C; Buckner, Frederick S et al.
In: MOLECULAR AND BIOCHEMICAL PARASITOLOGY, Vol. 126, No. 2, 02.2003, p. 155-63.

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

TY - JOUR

T1 - Protein farnesyl and N-myristoyl transferases

T2 - piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics

AU - Gelb, Michael H

AU - Van Voorhis, Wesley C

AU - Buckner, Frederick S

AU - Yokoyama, Kohei

AU - Eastman, Richard

AU - Carpenter, Elisabeth P

AU - Panethymitaki, Chrysoula

AU - Brown, Katherine A

AU - Smith, Deborah F

PY - 2003/2

Y1 - 2003/2

N2 - To accelerate progress in the development of therapeutics for protozoan parasitic diseases, we are studying enzymes active in co- and post-translational protein modification that are already the focus of drug development in other eukaryotic systems. Inhibitors of the protein farnesyltransferases (PFT) are well-established antitumour agents of low cytotoxicity and known pharmokinetic properties, while inhibitors of N-myristoyl transferase show both selectivity and specificity in the treatment of fungal infections. Here, we summarise the current evidence that supports the targeting of these ubiquitous eukaryotic enzymes for drug development against trypanosomatid infections and malaria.

AB - To accelerate progress in the development of therapeutics for protozoan parasitic diseases, we are studying enzymes active in co- and post-translational protein modification that are already the focus of drug development in other eukaryotic systems. Inhibitors of the protein farnesyltransferases (PFT) are well-established antitumour agents of low cytotoxicity and known pharmokinetic properties, while inhibitors of N-myristoyl transferase show both selectivity and specificity in the treatment of fungal infections. Here, we summarise the current evidence that supports the targeting of these ubiquitous eukaryotic enzymes for drug development against trypanosomatid infections and malaria.

KW - Acyltransferases

KW - Alkyl and Aryl Transferases

KW - Animals

KW - Antimalarials

KW - Chemistry, Pharmaceutical

KW - Drug Design

KW - Plasmodium

KW - Protein Conformation

KW - Trypanocidal Agents

KW - Trypanosoma

M3 - Article

C2 - 12615314

SN - 0166-6851

VL - 126

SP - 155

EP - 163

JO - MOLECULAR AND BIOCHEMICAL PARASITOLOGY

JF - MOLECULAR AND BIOCHEMICAL PARASITOLOGY

IS - 2

ER -