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Concentration- and ...
Concentration- and pH-Dependent Oligomerization of the Thrombin-Derived C-Terminal Peptide TCP-25.
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- Petruk, Ganna (författare)
- Lund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Petrlova, Jitka (författare)
- Lund University,Lunds universitet,Schmidtchen lab,Forskargrupper vid Lunds universitet,Schmidtchen Lab,Lund University Research Groups
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- Samsudin, Firdaus (författare)
- Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore
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- Del Giudice, Rita, 1985- (författare)
- Malmö University,Malmö universitet,Biofilms Research Center for Biointerfaces,Institutionen för biomedicinsk vetenskap (BMV)
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- Bond, Peter J (författare)
- Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore
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- Schmidtchen, Artur (författare)
- Lund University,Lunds universitet,Schmidtchen lab,Forskargrupper vid Lunds universitet,Schmidtchen Lab,Lund University Research Groups,University of Copenhagen,Bispebjerg Hospital,Skåne University Hospital
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(creator_code:org_t)
- 2020-11-19
- 2020
- Engelska.
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 10:11
- Relaterad länk:
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https://doi.org/10.3...
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https://mau.diva-por... (primary) (Raw object)
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https://www.mdpi.com...
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Peptide oligomerization dynamics affects peptide structure, activity, and pharmacodynamic properties. The thrombin C-terminal peptide, TCP-25 (GKYGFYTHVFRLKKWIQKVIDQFGE), is currently in preclinical development for improved wound healing and infection prevention. It exhibits turbidity when formulated at pH 7.4, particularly at concentrations of 0.3 mM or more. We used biochemical and biophysical approaches to explore whether the peptide self-associates and forms oligomers. The peptide showed a dose-dependent increase in turbidity as well as α-helical structure at pH 7.4, a phenomenon not observed at pH 5.0. By analyzing the intrinsic tryptophan fluorescence, we demonstrate that TCP-25 is more stable at high concentrations (0.3 mM) when exposed to high temperatures or a high concentration of denaturant agents, which is compatible with oligomer formation. The denaturation process was reversible above 100 µM of peptide. Dynamic light scattering demonstrated that TCP-25 oligomerization is sensitive to changes in pH, time, and temperature. Computational modeling with an active 18-mer region of TCP-25 showed that the peptide can form pH-dependent higher-order end-to-end oligomers and micelle-like structures, which is in agreement with the experimental data. Thus, TCP-25 exhibits pH- and temperature-dependent dynamic changes involving helical induction and reversible oligomerization, which explains the observed turbidity of the pharmacologically developed formulation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- TCP-25
- antimicrobial peptide
- oligomerization
- pH- and/or concentration-sensitive oligomerization
- peptide self-assembly
- thrombin
- Antimicrobial peptide
- Oligomerization
- Peptide self-assembly
- pH-and/or concentration-sensitive oligomerization
- TCP-25
- Thrombin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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