Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: New leads for antifungal and anti-inflammatory drugs

Mark J Dixon; Amit Nathubhai; Ole A Andersen; Daan M F van Aalten; Ian M Eggleston

doi:10.1007/978-0-387-73657-0_229

Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: New leads for antifungal and anti-inflammatory drugs

Mark J Dixon, Amit Nathubhai, Ole A Andersen, Daan M F van Aalten, Ian M Eggleston

Research output: Contribution to Book/Report › Conference Contribution › peer-review

Abstract

Family 18 chitinases play key roles in the life cycles of many organisms that are pathogenic to humans, such as fungi, bacteria, and parasitic nematodes. The onset or transmission of several major human diseases (e.g. malaria, filariasis) has been linked with the activity of chitinases from such organisms, while the overexpression of endogeneous mammalian chitinases, notwithstanding the absence of chitin from mammalian physiology, is a significant feature in asthma and lipid storage disorders such as Gaucher’s disease [1]. Selective inhibitors of these enzymes are of great interest as new drug leads or biochemical probes, and in this context, we recently reported the first syntheses of two cyclic peptide natural products, argifin [2] and argadin [3], that show nanomolar inhibition of a range of family 18 chitinases.

Original language	English
Title of host publication	Peptides for Youth
Subtitle of host publication	The Proceedings of the 20th American Peptide Symposium
Editors	Susan Del Valle, Emanuel Escher, William Lubell
Publisher	Springer Verlag
Pages	525-6
Number of pages	2
Volume	611
ISBN (Electronic)	978-0-387-73657-0
ISBN (Print)	978-0-387-73656-3, 978-1-4614-9829-2
DOIs	https://doi.org/10.1007/978-0-387-73657-0_229
Publication status	Published - 26 Mar 2009
Externally published	Yes

Keywords

Anti-Inflammatory Agents/chemical synthesis
Antifungal Agents/chemical synthesis
Cell Line, Tumor
Chitinases/antagonists & inhibitors
Drug Evaluation, Preclinical
Electrophoresis, Polyacrylamide Gel
Enzyme Inhibitors/chemical synthesis
Humans
Peptides, Cyclic/chemical synthesis
Photoaffinity Labels
Structure-Activity Relationship

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10.1007/978-0-387-73657-0_229

Cite this

Dixon, M. J., Nathubhai, A., Andersen, O. A., van Aalten, D. M. F., & Eggleston, I. M. (2009). Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: New leads for antifungal and anti-inflammatory drugs. In S. Del Valle, E. Escher, & W. Lubell (Eds.), Peptides for Youth: The Proceedings of the 20th American Peptide Symposium (Vol. 611, pp. 525-6). Springer Verlag. https://doi.org/10.1007/978-0-387-73657-0_229

Dixon, Mark J ; Nathubhai, Amit ; Andersen, Ole A et al. / Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors : New leads for antifungal and anti-inflammatory drugs. Peptides for Youth: The Proceedings of the 20th American Peptide Symposium. editor / Susan Del Valle ; Emanuel Escher ; William Lubell. Vol. 611 Springer Verlag, 2009. pp. 525-6

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title = "Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: New leads for antifungal and anti-inflammatory drugs",

abstract = "Family 18 chitinases play key roles in the life cycles of many organisms that are pathogenic to humans, such as fungi, bacteria, and parasitic nematodes. The onset or transmission of several major human diseases (e.g. malaria, filariasis) has been linked with the activity of chitinases from such organisms, while the overexpression of endogeneous mammalian chitinases, notwithstanding the absence of chitin from mammalian physiology, is a significant feature in asthma and lipid storage disorders such as Gaucher{\textquoteright}s disease [1]. Selective inhibitors of these enzymes are of great interest as new drug leads or biochemical probes, and in this context, we recently reported the first syntheses of two cyclic peptide natural products, argifin [2] and argadin [3], that show nanomolar inhibition of a range of family 18 chitinases. ",

keywords = "Anti-Inflammatory Agents/chemical synthesis, Antifungal Agents/chemical synthesis, Cell Line, Tumor, Chitinases/antagonists & inhibitors, Drug Evaluation, Preclinical, Electrophoresis, Polyacrylamide Gel, Enzyme Inhibitors/chemical synthesis, Humans, Peptides, Cyclic/chemical synthesis, Photoaffinity Labels, Structure-Activity Relationship",

author = "Dixon, {Mark J} and Amit Nathubhai and Andersen, {Ole A} and {van Aalten}, {Daan M F} and Eggleston, {Ian M}",

year = "2009",

month = mar,

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doi = "10.1007/978-0-387-73657-0_229",

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Dixon, MJ, Nathubhai, A, Andersen, OA, van Aalten, DMF & Eggleston, IM 2009, Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: New leads for antifungal and anti-inflammatory drugs. in S Del Valle, E Escher & W Lubell (eds), Peptides for Youth: The Proceedings of the 20th American Peptide Symposium. vol. 611, Springer Verlag, pp. 525-6. https://doi.org/10.1007/978-0-387-73657-0_229

Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: New leads for antifungal and anti-inflammatory drugs. / Dixon, Mark J; Nathubhai, Amit; Andersen, Ole A et al.
Peptides for Youth: The Proceedings of the 20th American Peptide Symposium. ed. / Susan Del Valle; Emanuel Escher; William Lubell. Vol. 611 Springer Verlag, 2009. p. 525-6.

Research output: Contribution to Book/Report › Conference Contribution › peer-review

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T1 - Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors

T2 - New leads for antifungal and anti-inflammatory drugs

AU - Dixon, Mark J

AU - Nathubhai, Amit

AU - Andersen, Ole A

AU - van Aalten, Daan M F

AU - Eggleston, Ian M

PY - 2009/3/26

Y1 - 2009/3/26

N2 - Family 18 chitinases play key roles in the life cycles of many organisms that are pathogenic to humans, such as fungi, bacteria, and parasitic nematodes. The onset or transmission of several major human diseases (e.g. malaria, filariasis) has been linked with the activity of chitinases from such organisms, while the overexpression of endogeneous mammalian chitinases, notwithstanding the absence of chitin from mammalian physiology, is a significant feature in asthma and lipid storage disorders such as Gaucher’s disease [1]. Selective inhibitors of these enzymes are of great interest as new drug leads or biochemical probes, and in this context, we recently reported the first syntheses of two cyclic peptide natural products, argifin [2] and argadin [3], that show nanomolar inhibition of a range of family 18 chitinases.

AB - Family 18 chitinases play key roles in the life cycles of many organisms that are pathogenic to humans, such as fungi, bacteria, and parasitic nematodes. The onset or transmission of several major human diseases (e.g. malaria, filariasis) has been linked with the activity of chitinases from such organisms, while the overexpression of endogeneous mammalian chitinases, notwithstanding the absence of chitin from mammalian physiology, is a significant feature in asthma and lipid storage disorders such as Gaucher’s disease [1]. Selective inhibitors of these enzymes are of great interest as new drug leads or biochemical probes, and in this context, we recently reported the first syntheses of two cyclic peptide natural products, argifin [2] and argadin [3], that show nanomolar inhibition of a range of family 18 chitinases.

KW - Anti-Inflammatory Agents/chemical synthesis

KW - Antifungal Agents/chemical synthesis

KW - Cell Line, Tumor

KW - Chitinases/antagonists & inhibitors

KW - Drug Evaluation, Preclinical

KW - Electrophoresis, Polyacrylamide Gel

KW - Enzyme Inhibitors/chemical synthesis

KW - Humans

KW - Peptides, Cyclic/chemical synthesis

KW - Photoaffinity Labels

KW - Structure-Activity Relationship

U2 - 10.1007/978-0-387-73657-0_229

DO - 10.1007/978-0-387-73657-0_229

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SN - 978-0-387-73656-3

SN - 978-1-4614-9829-2

VL - 611

SP - 525

EP - 526

BT - Peptides for Youth

A2 - Del Valle, Susan

A2 - Escher, Emanuel

A2 - Lubell, William

PB - Springer Verlag

ER -

Dixon MJ, Nathubhai A, Andersen OA, van Aalten DMF, Eggleston IM. Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: New leads for antifungal and anti-inflammatory drugs. In Del Valle S, Escher E, Lubell W, editors, Peptides for Youth: The Proceedings of the 20th American Peptide Symposium. Vol. 611. Springer Verlag. 2009. p. 525-6 doi: 10.1007/978-0-387-73657-0_229

Synthesis and structure-based dissection of cyclic peptide chitinase inhibitors: New leads for antifungal and anti-inflammatory drugs

Abstract

Keywords

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