Improved synthesis and biological evaluation of chelator-modified α-MSH analogs prepared by copper-free click chemistry

Nicholas J Baumhover; Molly E Martin; Sharavathi G Parameswarappa; Kyle C Kloepping; M. Sue O’Dorisio; F. Christopher Pigge; Michael K Schultz

doi:10.1016/j.bmcl.2011.08.017

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Improved synthesis and biological evaluation of chelator-modified α-MSH analogs prepared by copper-free click chemistry

Journal article

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Peer reviewed

Improved synthesis and biological evaluation of chelator-modified α-MSH analogs prepared by copper-free click chemistry

Nicholas J Baumhover, Molly E Martin, Sharavathi G Parameswarappa, Kyle C Kloepping, M. Sue O’Dorisio, F. Christopher Pigge and Michael K Schultz

Bioorganic & medicinal chemistry letters, Vol.21(19), pp.5757-5761

2011

DOI: 10.1016/j.bmcl.2011.08.017

PMCID: PMC3171621

PMID: 21873053

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Abstract

Radionuclide chelators (DOTA, NOTA) functionalized with a monofluorocyclooctyne group were prepared. These materials reacted rapidly and in high yield with a fully deprotected azide-modified peptide via Cu-free click chemistry under mild reaction conditions (aqueous solution, room temperature). The resulting bioconjugates bind with high affinity and specificity to their cell-surface receptor targets in vitro and appear stable to degradation in mouse serum over 3 h of incubation at 37 °C.

Molecular imaging

Copper free click chemistry

PRRT

Gallium-68

Copper-64

Melanocyte stimulating hormone

Radionuclide therapy

Peptide synthesis

Cyclooctyne

PET

Details

Title: Subtitle: Improved synthesis and biological evaluation of chelator-modified α-MSH analogs prepared by copper-free click chemistry
Creators: Nicholas J Baumhover - Department of Radiology, Carver College of Medicine, The University of Iowa, 500 Newton Road, ML B180, Iowa City, IA 52242, USA
Molly E Martin - Department of Pediatric Hematology/Oncology, Carver College of Medicine, The University of Iowa Research Park, B145 MTF, 2501 Crosspark Road, Coralville, IA 52241, USA
Sharavathi G Parameswarappa - Department of Chemistry, The University of Iowa, E557 CB, Iowa City, IA 52242, USA
Kyle C Kloepping - Department of Radiology, Carver College of Medicine, The University of Iowa, 500 Newton Road, ML B180, Iowa City, IA 52242, USA
M. Sue O’Dorisio - Department of Pediatric Hematology/Oncology, Carver College of Medicine, The University of Iowa Research Park, B145 MTF, 2501 Crosspark Road, Coralville, IA 52241, USA
F. Christopher Pigge - Department of Chemistry, The University of Iowa, E557 CB, Iowa City, IA 52242, USA
Michael K Schultz - Department of Radiology, Carver College of Medicine, The University of Iowa, 500 Newton Road, ML B180, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Bioorganic & medicinal chemistry letters, Vol.21(19), pp.5757-5761
DOI: 10.1016/j.bmcl.2011.08.017
PMID: 21873053
PMCID: PMC3171621
NLM abbreviation: Bioorg Med Chem Lett
ISSN: 0960-894X
eISSN: 1464-3405
Publisher: Elsevier Ltd
Language: English
Date published: 2011
Academic Unit: Radiology; Stead Family Department of Pediatrics; Radiation Oncology; Pharmacy Practice and Science; Chemistry
Record Identifier: 9983985702102771

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