Combinatorial Library Screening with Liposomes for Discovery of Membrane Active Peptides
| Autor: | Mary Saunders, Amir Sahabi, David J. Olivos, Randy P. Carney, Lin Tian, Yann Thillier, Zsofia Kiss, Alisha Knudson, Ruiwu Liu, Kit S. Lam, Jean Carlos Heleno Campos |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
liposomes
0301 basic medicine endosomal escape capabilities Endosome Surface Properties Bioengineering Computational biology Cell-Penetrating Peptides 010402 general chemistry 01 natural sciences Article Cell Line Medicinal and Biomolecular Chemistry 03 medical and health sciences Peptide Library High-Throughput Screening Assays Combinatorial Chemistry Techniques Humans Amino Acids Peptide library high-throughput Fluorescent Dyes drug delivery platforms chemistry.chemical_classification Liposome Rhodamines Biomolecule Organic Chemistry General Chemistry General Medicine membrane-active proteins Hydrogen-Ion Concentration Combinatorial chemistry Microspheres 0104 chemical sciences 030104 developmental biology Membrane chemistry 5.1 Pharmaceuticals Liposomes Generic health relevance Development of treatments and therapeutic interventions one-bead-one-compound Intracellular Biotechnology |
| Zdroj: | ACS combinatorial science, vol 19, iss 5 |
| Popis: | Membrane active peptides (MAPs) represent a class of short biomolecules that have shown great promise in facilitating intracellular delivery without disrupting cellular plasma membranes. Yet their clinical application has been stalled by numerous factors: off-target delivery, a requirement for high local concentration near cells of interest, degradation en route to the target site, and in the case of cell-penetrating peptides, eventual entrapment in endolysosomal compartments. The current method of deriving MAPs from naturally occurring proteins has restricted the discovery of new peptides that may overcome these limitations. Here, we describe a new branch of assays featuring high-throughput functional screening capable of discovering new peptides with tailored cell uptake and endosomal escape capabilities. The one-bead-one-compound (OBOC) combinatorial method is used to screen libraries containing millions of potential MAPs for binding to synthetic liposomes, which can be adapted to mimic various aspects of limiting membranes. By incorporating unnatural and d-amino acids in the library, in addition to varying buffer conditions and liposome compositions, we have identified several new highly potent MAPs that improve on current standards and introduce motifs that were previously unknown or considered unsuitable. Since small variations in pH and lipid composition can be controlled during screening, peptides discovered using this methodology could aid researchers building drug delivery platforms with unique requirements, such as targeted intracellular localization. |
| Databáze: | OpenAIRE |
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