Synthesis and evaluation of novel lipopeptide as a vehicle for efficient gene delivery and gene silencing

Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

“…Depending on these characteristics, the thermophoresis behavior of the complex compound is significantly different from single molecule. During the whole experiment, the concentration of fluorescent-labeled molecules (FITC-labeled hIAPP [11][12][13][14][15][16][17][18][19][20] is fixed, while the nonfluorescent molecules (inhibitors) solutions are diluted by gradient. Consequently, MST not only possesses high stability of fluorescence spectrum methods but also has high sensitivity of thermophoresis, providing a comparable approach on studying biomolecular interactions.…”

“…Fluorescence measurement was conducted to monitor the extent of fibril formation of hIAPP [11][12][13][14][15][16][17][18][19][20] by LS55 Fluorescence Spectrofluorometer system (PerkinElmer Inc, UK). Time curves of thermophoresis for binding affinity were obtained on the microscale thermophoresis (MST) setup (Monolith NT.115 system, NanoTemper Technologies GmbH, Germany).…”

“…As lipopeptides have some hydrophobic groups, which are similar to the reported aggregation inhibitors, and some lipopeptides could prevent cells from depositing of amyloid fibrils, several potential lipopeptide inhibitors have been engineered and synthesized, which have been assessed for their inhibitory effect in preventing amyloid fibrils formation of hIAPP [11][12][13][14][15][16][17][18][19][20] by using the conventional thioflavin-T fluorescence assay and new technique microscale thermophoresis (MST). The final amyloid fibrils of hIAPP [11][12][13][14][15][16][17][18][19][20] were characterized by transmission electron microscopy. Results suggested that with the increasing length of alkyl chain, the antiaggregation efficiency of lipopeptide inhibitors towards hIAPP 11-20 increased gradually.…”

“…On the basis of our previous study about different synthesized peptides modulating the self-assembly [30] of hIAPP [11][12][13][14][15][16][17][18][19][20] , most of the inhibitors that could effectively inhibit amyloid formation possess hydrophobic amino acids. Hence, in this study, several potential lipopeptide inhibitors containing hydrophobic alkyl chains and hydrophilic amino acids as head group have been engineered and synthesized, Cx-RRRR-NH 2 (x = 4, 6, 8, 10, 12, and 14; lipopeptides with x carbon atoms) and C14-Rn-NH 2 (n = 2, 3, 4, and 5; lipopeptides with n arginines) ( Figure 1).…”

“…Hence, in this study, several potential lipopeptide inhibitors containing hydrophobic alkyl chains and hydrophilic amino acids as head group have been engineered and synthesized, Cx-RRRR-NH 2 (x = 4, 6, 8, 10, 12, and 14; lipopeptides with x carbon atoms) and C14-Rn-NH 2 (n = 2, 3, 4, and 5; lipopeptides with n arginines) ( Figure 1). The extent of hIAPP [11][12][13][14][15][16][17][18][19][20] fibrilization under the influence of these inhibitors was assessed, and the binding events between amyloidogenic peptides and inhibitors were investigated. This study will help to deduce a rational template of lipopeptide inhibitor design for hIAPP.…”