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Gastroresistant oral peptide for fluorescence imaging of colonic inflammation


Luciani, Paola; Estella-Hermoso de Mendoza, Ander; Casalini, Tommaso; Lang, Silvia; Atrott, Kirstin; Spalinger, Marianne R; Pratsinis, Anna; Sobek, Jens; Frey-Wagner, Isabelle; Schumacher, Jens; Leroux, Jean-Christophe; Rogler, Gerhard (2017). Gastroresistant oral peptide for fluorescence imaging of colonic inflammation. Journal of Controlled Release, 262:118-126.

Abstract

The use of molecular markers for inflammation in the gastrointestinal tract could empower optical imaging modalities for early diagnosis and eventually personalized timely treatments. A major hurdle to the widespread use of functional fluorescence imaging is the absence of suitable contrast agents, in particular to be administered via the oral route due to the usual proteolytic susceptibility of the biomarkers. By designing a retro-inverso peptide, starting from a previously described sequence specific for N-cadherin, we achieved resistance to gastrointestinal degradation and even slightly improved specificity towards the target, both in ex vivo and in vivo experimental colitis. Simulations at fundamental molecular level suggested that the introduced retro-inverso modifications did not affect the folding of the peptide, leaving its ability to interact with the binding pocket of the monomeric N-cadherin unaltered, even when fluorescently labeled. Possible further derivatization of this sequence could be envisaged to further extend the potential of the designed retro-inverso peptide as diagnostic or theranostic agent for the oral route.

Abstract

The use of molecular markers for inflammation in the gastrointestinal tract could empower optical imaging modalities for early diagnosis and eventually personalized timely treatments. A major hurdle to the widespread use of functional fluorescence imaging is the absence of suitable contrast agents, in particular to be administered via the oral route due to the usual proteolytic susceptibility of the biomarkers. By designing a retro-inverso peptide, starting from a previously described sequence specific for N-cadherin, we achieved resistance to gastrointestinal degradation and even slightly improved specificity towards the target, both in ex vivo and in vivo experimental colitis. Simulations at fundamental molecular level suggested that the introduced retro-inverso modifications did not affect the folding of the peptide, leaving its ability to interact with the binding pocket of the monomeric N-cadherin unaltered, even when fluorescently labeled. Possible further derivatization of this sequence could be envisaged to further extend the potential of the designed retro-inverso peptide as diagnostic or theranostic agent for the oral route.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:28 September 2017
Deposited On:19 Jan 2018 08:04
Last Modified:19 Feb 2018 10:23
Publisher:Elsevier
ISSN:0168-3659
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.jconrel.2017.07.024
PubMed ID:28734901

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