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dc.contributor.authorChan, Kiat Hwa
dc.contributor.authorLee, Wei Hao
dc.contributor.authorNi, Ming
dc.contributor.authorLoo, Yihua
dc.contributor.authorHauser, Charlotte
dc.date.accessioned2018-11-21T13:09:37Z
dc.date.available2018-11-21T13:09:37Z
dc.date.issued2018-11-20
dc.identifier.citationChan KH, Lee WH, Ni M, Loo Y, Hauser CAE (2018) C-Terminal Residue of Ultrashort Peptides Impacts on Molecular Self-Assembly, Hydrogelation, and Interaction with Small-Molecule Drugs. Scientific Reports 8. Available: http://dx.doi.org/10.1038/s41598-018-35431-2.
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-018-35431-2
dc.identifier.urihttp://hdl.handle.net/10754/629933
dc.description.abstractSingle molecular changes on a tripeptide can have dramatic effects on their self-assembly and hydrogelation. Herein, we explore C-terminal residue variation on two consistent ultrashort peptide backbones, i.e. acetylated-Leu-Ile-Val-Ala-Gly-Xaa and acetylated-Ile-Val-Xaa (Xaa = His, Arg, Asn). The objective of this study is to identify candidates that can form hydrogels for small-molecule drug (SMD) delivery. Haemolysis and cytotoxicity (with human adipose-derived mesenchymal stem cells) assays showed that the new soluble peptides (Xaa = His, Arg) are cytocompatible. Gelation studies showed that all but acetylated-Ile-Val-Arg could gel under physiological conditions. Longer peptidic backbones drive self-assembly more effectively as reflected in field emission scanning electron microscopy (FESEM) and circular dichroism spectroscopy studies. Rheological studies revealed that the resultant hydrogels have varying stiffness and yield stress, depending on the backbone and C-terminal residue. Visible spectroscopy-based elution studies with SMDs (naltrexone, methotrexate, doxorubicin) showed that besides the C-terminal residue, the shape of the SMD also determines the rate and extent of SMD elution. Based on the elution assays, infrared spectroscopy, and FESEM, we propose models for the peptide fibril-SMD interaction. Our findings highlight the importance of matching the molecular properties of the self-assembling peptide and SMD in order to achieve the desired SMD release profile.
dc.description.sponsorshipThis work was supported by Yale-National University of Singapore (Yale-NUS) College, the Institute of Bioengineering (Biomedical Research Council, Agency of Science, Technology and Research, Singapore) and King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia. The authors would like to thank Associate Professor Thiam Chye Lim of the National University Hospital for a gift of hASCs.
dc.publisherSpringer Nature
dc.relation.urlhttps://www.nature.com/articles/s41598-018-35431-2
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleC-Terminal Residue of Ultrashort Peptides Impacts on Molecular Self-Assembly, Hydrogelation, and Interaction with Small-Molecule Drugs
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
dc.contributor.departmentLaboratory for Nanomedicine, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia
dc.identifier.journalScientific Reports
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDivision of Science, Yale-NUS College, 16 College Avenue West, Singapore, 138527, Singapore
dc.contributor.institutionDepartment of Chemistry, Krieger School of Arts & Sciences, 3400 North Charles Street, Johns Hopkins University, Baltimore, Maryland, USA
dc.contributor.institutionSchool of Biological Sciences & Engineering, Yachay Tech University, Hacienda San José s/n, San Miguel de Urcuquí, 100105, Ecuador
dc.contributor.institutionInstitute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore
kaust.personHauser, Charlotte
refterms.dateFOA2018-11-22T11:34:16Z
dc.date.published-online2018-11-20
dc.date.published-print2018-12


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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.