Cargando…

Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis

The exposure of phosphatidylserine (PS) molecules from the inner to the outer leaflet of the plasma membrane has been recognized as a well-defined molecular epitope of cells undergoing apoptosis. Examination and monitoring of PS exposure is an extensively used molecular marker in non-invasive apopto...

Descripción completa

Detalles Bibliográficos
Autores principales: Thapa, Narendra, Kim, Soyoun, So, In-Sup, Lee, Byung-Heon, Kwon, Ick-Chan, Choi, Kuiwon, Kim, In-San
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918081/
https://www.ncbi.nlm.nih.gov/pubmed/18363834
http://dx.doi.org/10.1111/j.1582-4934.2008.00305.x
_version_ 1782302922067935232
author Thapa, Narendra
Kim, Soyoun
So, In-Sup
Lee, Byung-Heon
Kwon, Ick-Chan
Choi, Kuiwon
Kim, In-San
author_facet Thapa, Narendra
Kim, Soyoun
So, In-Sup
Lee, Byung-Heon
Kwon, Ick-Chan
Choi, Kuiwon
Kim, In-San
author_sort Thapa, Narendra
collection PubMed
description The exposure of phosphatidylserine (PS) molecules from the inner to the outer leaflet of the plasma membrane has been recognized as a well-defined molecular epitope of cells undergoing apoptosis. Examination and monitoring of PS exposure is an extensively used molecular marker in non-invasive apoptosis imaging under a variety of clinical conditions, including the assessment of therapeutic anti-cancer agents and myocardial infarction. Herein, we report the identification of a PS-recognizing peptide which was identified by the screening of an M13 phage display peptide library onto PS-coated ELISA plates. Repeated biopanning for a total of four rounds revealed a predominant enrichment of the phage clone displaying peptide sequence, CLSYYPSYC (46%). The identified phage clone evidenced enhanced binding to a number of apoptotic cells over non-apoptotic cells, and this binding was inhibited by both annexin V and synthesized peptide displayed on the phage. The binding of the fluorescein-labelled CLSYYPSYC peptide to apoptotic versus normal cells was assessed by both FACS analysis and fluorescence microscopy. Optical imaging after the systemic administration of fluorescein-labelled CLSYYPSYC peptide to tumour-bearing nude mice (H460 cells xenograft model) treated with a single dose of an anticancer drug (camp-tothecin) indicated peptide homing to the tumour. The histological examination of tumour tissues showed intense staining of the tumour vasculature and apoptotic tumour cells. With these results, the CLSYYPSYC peptide is recognized as a novel PS-recognizing moiety which may possibly be developed into a molecular probe for the imaging of apoptosis in vivo. This application would clearly be relevant to assessments of the efficacy of anticancer therapy in tumours.
format Online
Article
Text
id pubmed-3918081
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-39180812015-04-27 Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis Thapa, Narendra Kim, Soyoun So, In-Sup Lee, Byung-Heon Kwon, Ick-Chan Choi, Kuiwon Kim, In-San J Cell Mol Med Articles The exposure of phosphatidylserine (PS) molecules from the inner to the outer leaflet of the plasma membrane has been recognized as a well-defined molecular epitope of cells undergoing apoptosis. Examination and monitoring of PS exposure is an extensively used molecular marker in non-invasive apoptosis imaging under a variety of clinical conditions, including the assessment of therapeutic anti-cancer agents and myocardial infarction. Herein, we report the identification of a PS-recognizing peptide which was identified by the screening of an M13 phage display peptide library onto PS-coated ELISA plates. Repeated biopanning for a total of four rounds revealed a predominant enrichment of the phage clone displaying peptide sequence, CLSYYPSYC (46%). The identified phage clone evidenced enhanced binding to a number of apoptotic cells over non-apoptotic cells, and this binding was inhibited by both annexin V and synthesized peptide displayed on the phage. The binding of the fluorescein-labelled CLSYYPSYC peptide to apoptotic versus normal cells was assessed by both FACS analysis and fluorescence microscopy. Optical imaging after the systemic administration of fluorescein-labelled CLSYYPSYC peptide to tumour-bearing nude mice (H460 cells xenograft model) treated with a single dose of an anticancer drug (camp-tothecin) indicated peptide homing to the tumour. The histological examination of tumour tissues showed intense staining of the tumour vasculature and apoptotic tumour cells. With these results, the CLSYYPSYC peptide is recognized as a novel PS-recognizing moiety which may possibly be developed into a molecular probe for the imaging of apoptosis in vivo. This application would clearly be relevant to assessments of the efficacy of anticancer therapy in tumours. Blackwell Publishing Ltd 2008-09 2008-03-17 /pmc/articles/PMC3918081/ /pubmed/18363834 http://dx.doi.org/10.1111/j.1582-4934.2008.00305.x Text en © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Articles
Thapa, Narendra
Kim, Soyoun
So, In-Sup
Lee, Byung-Heon
Kwon, Ick-Chan
Choi, Kuiwon
Kim, In-San
Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis
title Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis
title_full Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis
title_fullStr Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis
title_full_unstemmed Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis
title_short Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis
title_sort discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918081/
https://www.ncbi.nlm.nih.gov/pubmed/18363834
http://dx.doi.org/10.1111/j.1582-4934.2008.00305.x
work_keys_str_mv AT thapanarendra discoveryofaphosphatidylserinerecognizingpeptideanditsutilityinmolecularimagingoftumourapoptosis
AT kimsoyoun discoveryofaphosphatidylserinerecognizingpeptideanditsutilityinmolecularimagingoftumourapoptosis
AT soinsup discoveryofaphosphatidylserinerecognizingpeptideanditsutilityinmolecularimagingoftumourapoptosis
AT leebyungheon discoveryofaphosphatidylserinerecognizingpeptideanditsutilityinmolecularimagingoftumourapoptosis
AT kwonickchan discoveryofaphosphatidylserinerecognizingpeptideanditsutilityinmolecularimagingoftumourapoptosis
AT choikuiwon discoveryofaphosphatidylserinerecognizingpeptideanditsutilityinmolecularimagingoftumourapoptosis
AT kiminsan discoveryofaphosphatidylserinerecognizingpeptideanditsutilityinmolecularimagingoftumourapoptosis