Self-assembling RATEA16 peptide nanofiber designed for rapid hemostasis

2020 ◽  
Vol 8 (9) ◽  
pp. 1897-1905 ◽  
Author(s):  
Shuda Wei ◽  
Fangping Chen ◽  
Zhen Geng ◽  
Ruihua Cui ◽  
Yujiao Zhao ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Self Assembly ◽  
Solid Phase ◽  
Phase Method ◽  
Self Assembling ◽  
Solid Phase Method ◽  
Assembly Performance

In this study, we synthesized a novel polypeptide material, RATEA16, by the solid phase method, and investigated the secondary structure, self-assembly performance, gelation ability, biocompatibility and hemostatic efficiency in vitro and in vivo.

Synthetic antagonists of the myometrial response to vasopressin and oxytocin

1986 ◽  
Vol 111 (1) ◽  
pp. 125-131 ◽  
Author(s):  
P. Melin ◽  
J. Trojnar ◽  
B. Johansson ◽  
H. Vilhardt ◽  
M. Åkerlund
Keyword(s):  
Blood Pressure ◽  
Pregnant Women ◽  
Solid Phase ◽  
Phase Method ◽  
Inhibitory Effects ◽  
Inhibitory Potency ◽  
Low Blood Pressure ◽  
Solid Phase Method

ABSTRACT With the aim of developing inhibitors of vasopressin-and oxytocin-induced uterine activity, 17 analogues of 1-deamino-oxytocin were synthesized by the solid-phase method. Modifications were made at positions 2, O-methyltyrosine (Tyr(OMe)) and O-ethyltyrosine (Tyr(OEt)),d-Tyr,d-Tyr(OEt),d-Trp; 4, Val,Thr and 8, Orn,Cit,Arg,d-Arg. The analogues were tested for antiuterotonic activity in vitro and in vivo in the rat and in vitro on myometrial strips from non-pregnant women and pregnant women at term. Their selectivity was also investigated in blood pressure and antidiuretic bioassays in rats. Results were compared with those from an original antiuterotonic analogue 1-deamino-2-Tyr(OEt)-oxytocin (d(OEt)-oxytocin). In the rat in vitro and in vivo all analogues possessed higher antiuterotonic activity than d(OEt)-oxytocin. The negative logarithm of the molar concentration of the antagonist which reduced the effect of a dose of agonist to that of half the dose (pA2) was between 7·6 and 8·9 for all the new inhibitors compared with 7·2 for d(OEt)-oxytocin. The highest pA2 value was found for 1-deamino-2-Tyr(OMe)-8-Orn-oxytocin (8·9 ± 0·2, s.e.m.) and 1-deamino-2-Tyr(OEt)-4-Thr-8-Orn-oxytocin (8·9 ± 0·6). In myometrium from non-pregnant women the most potent peptide was 1-deamino-2-d-Tyr(OEt)-4-Th r-8-Orn-oxytocin (17·2 ± 2·0 times more potent that d(OEt)-oxytocin). In myometrium from pregnant women the inhibitory effects of the majority of the analogues were less pronounced. In the rat in vivo the most potent analogue 1-deamino-2-d-Trp-4-Val-8-Orn-oxytocin was 19·9 ± 2·5 times more active than d(OEt)-oxytocin. Exchanging l-tyrosine for the d form generally increased inhibitory activity as well as specificity of the analogues. Alkylation of the d-tyrosine residue did not appear to be necessary for inhibition. Substitution with d-tryptophan at position 2 gave analogues with high inhibitory potency in the rat in vitro and in vivo, but which exhibited weak effects in women in vitro. There was no correlation between the inhibitory effects on myometrium from non-pregnant and pregnant women nor between rat and human data. The high antiuterotonic activity of 1-deamino-2-d-Tyr(OEt)-4-Val-8-Orn-oxytocin and 1-deamino-2-d-Tyr(OEt)-4-Thr-8-Orn-oxytocin combined with low blood pressure and antidiuretic effects make these two analogues interesting for clinical studies. J. Endocr. (1986) 111, 125–131

The Analogs of [D-Har8]Vasopressin with Di- and Trisubstituted Phenylalanine in Position 2; Synthesis and Some Biological Properties

1993 ◽  
Vol 58 (11) ◽  
pp. 2751-2760 ◽  
Author(s):  
Miroslava Žertová ◽  
Zdenko Procházka ◽  
Jiřina Slaninová ◽  
Tomislav Barth ◽  
Pavel Majer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Biological Properties ◽  
Phase Method ◽  
Antidiuretic Activity ◽  
Solid Phase Method

Four analogs of vasopressin with non-coded amino acids D-homoarginine (in position 8) and 2,6-di- or 2,4,6-trisubstituted L- or D-phenylalanine (in position 2) were synthesized using the solid phase method on p-methylbenzhydrylamine resin. All the analogs were found to be uterotonic inhibitors, the most potent one in vitro and in vivo being [D-Phe(2,4,6-triMe)2,D-Har8]vasopressin with pA2 values equal to 8.1 and 7.5, respectively. All of them had negligible antidiuretic activity and were weak pressor inhibitors.

Synthesis of peptides by the solid-phase method. V. Substance P and analogs

1980 ◽  
Vol 58 (4) ◽  
pp. 272-280 ◽  
Author(s):  
A. Fournier ◽  
R. Couture ◽  
J. Magnan ◽  
M. Gendreau ◽  
D. Regoli ◽  
...  
Keyword(s):  
Substance P ◽  
Solid Phase ◽  
Gel Filtration ◽  
Paper Electrophoresis ◽  
Exchange Chromatography ◽  
Phase Method ◽  
Elemental Analyses ◽  
Solid Phase Method

We have synthesized a series of 12 analogs of the undecapeptide substance P in order to perform a structure–activity study of this peptide. In the present work, each residue was substituted by L-alanine, and the C-terminal amide was replaced by the free carboxyl in order to pinpoint biologically important side chains and functional groups. The synthesis of the analogs was carried out by the automatic solid-phase method. Couplings were performed by the symmetrical anhydride procedure. After cleavage with liquid HF, the peptides were purified by gel filtration and ion-exchange chromatography. Their purity was assessed by thin-layer chromatography, paper electrophoresis, amino acid and elemental analyses, and high pressure liquid chromatography. They were tested for biological activity in vitro on the ileum of the guinea pig, the mesenteric vein of the rabbit, and the vas deferens of the rat, and in vivo by measuring their effect on the blood pressure of the rat.

scholarly journals Lipid membranes trigger misfolding and self-assembly of amyloid β 42 protein into aggregates

2019 ◽  
Author(s):  
Siddhartha Banerjee ◽  
Mohtadin Hashemi ◽  
Karen Zagorski ◽  
Yuri L. Lyubchenko
Keyword(s):  
Self Assembly ◽  
Lipid Membranes ◽  
Membrane Surface ◽  
Amyloid Β ◽  
Test Tube ◽  
Aggregation Process ◽  
Self Assembling ◽  
Nanoscale Aggregates

AbstractThe assembly of polypeptides and proteins into nanoscale aggregates is a phenomenon observed in a vast majority of proteins. Importantly, aggregation of amyloid β (Aβ) proteins is considered as a major cause for the development of Alzheimer’s disease. The process depends on various conditions and typical test-tube experiments require high protein concentration that complicates the translation of results obtained in vitro to understanding the aggregation process in vivo. Here we demonstrate that Aβ42 monomers at the membrane bilayer are capable of self-assembling into aggregates at physiologically low concentrations, and the membrane in this aggregation process plays a role of a catalyst. We applied all-atom molecular dynamics to demonstrate that the interaction with the membrane surface dramatically changes the conformation of Aβ42 protein. As a result, the misfolded Aβ42 rapidly assembles into dimers, trimers and tetramers, so the on-surface aggregation is the mechanism by which amyloid oligomers are produced and spread.

Conjugates of Hepatitis B Surface Antigen (14-32)Pre-S2 Region with N-Acetylmuramic Acid, N-Acetylnormuramic Acid, and Their L-Alanyl-D-Isoglutamine Derivatives: Synthesis and Studies on Immunogenicity

1992 ◽  
Vol 57 (1) ◽  
pp. 204-211
Author(s):  
Zbigniev Maćkiewicz ◽  
Hanna Świderska ◽  
Maria Kalmanowa ◽  
Zygfryd Smiatacz ◽  
Adam Nowosławski ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Solid Phase ◽  
Hepatitis B Surface Antigen ◽  
Phase Method ◽  
Virus Surface ◽  
Solid Phase Method ◽  
Cellular And Humoral Immunity ◽  
Cellular Immune

Four novel analogs of hepatitis B virus surface antigen (14-32)Pre-S2 region fragment attached covalently to N-acetylmuramic acid, N-acetylmuramyl-L-alanyl-D-isoglutamine, N-acetylnormuramic acid, and N-acetylnormuramyl-L-alanyl-D-isoglutamine were synthesized by the solid phase method. The ability of analogs to induce cellular and humoral immunity to native HBsAg was tested on rabbits. Cellular immune response occurred in vitro, and HBs antibodies were detected in all immunized animals. No additional adjuvants were used in the tests.

Targeted Chemotherapy for Breast Cancer Using an Intelligent Doxorubicin-Loaded Hexapeptide Hydrogel

2020 ◽  
Vol 16 (6) ◽  
pp. 842-852
Author(s):  
Shiyao Luo ◽  
Ying Zhu ◽  
Yiping Li ◽  
Li Chen ◽  
Shunzhong Lv ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Solid Phase ◽  
Synthesis Method ◽  
High Water ◽  
High Water Content ◽  
Normal Tissues ◽  
Self Assembling ◽  
Peptide Hydrogel

Self-assembling peptide hydrogels have a high water content, good biocompatibility and have become a competitive research object in the fields of tissue engineering, cancer treatment and drug delivery. In our research, a hexapeptide with high pH sensitivity was designed and synthesized by utilizing a solid-phase synthesis method. Under physiological conditions, the peptide could self-assemble into a hydrogel. When it reached the tumor acidic microenvironment, the peptide was degraded and doxorubicin was released to exert its antitumor effect. A series of physicochemical properties were investigated, including gelling ability, secondary structure, micromorphology, rheological properties and drug release studies. The results illustrated that PIDO peptide hydrogel has good pH responsiveness and injectability. In vitro cytotoxicity experiments and in vivo antitumor experiments showed that PIDO peptide hydrogel has a highly effective therapeutic effect on tumor cells and is less toxic to normal tissues. Our research provides a promising option for targeted drug delivery and sustainable release.

Molecular self-assembly of a tyroservatide-derived octapeptide and hydroxycamptothecin for enhanced therapeutic efficacy

Nanoscale ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 5094-5102
Author(s):  
Jing Liu ◽  
Can Wu ◽  
Guoru Dai ◽  
Feng Feng ◽  
Yuquan Chi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Self Assembly ◽  
Therapeutic Efficacy ◽  
Self Assembling

A pure l-amino acid-based molecular hydrogel was designed through conjugation of an anticancer tripeptide tyroservatide (YSV) with a self-assembling moiety, which enhanced therapeutic efficacy of both YSV and hydroxycamptothecin in vitro and in vivo.

Antagonistic Analogs of Oxytocin with Substituted Phenylalanine or Tyrosine in Position 2

1994 ◽  
Vol 59 (6) ◽  
pp. 1430-1438 ◽  
Author(s):  
Rudolf Ježek ◽  
Miroslava Žertová ◽  
Jiřina Slaninová ◽  
Pavel Majer ◽  
Zdenko Procházka
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Phase Method ◽  
Inhibiting Activity ◽  
Structure Activity ◽  
Low Degree ◽  
Solid Phase Method ◽  
Pressor Activity ◽  
Agonistic Activity

Solid phase method on p-methylbenzhydrylamine resin was used for the synthesis of seven analogs of oxytocin with non-coded amino acids in position 2. [L-Phe(4-Me)2]oxytocin (I), [D-Phe(4-Me)2]oxytocin (II), [L-Phe(2-Me,4-Et)2]oxytocin (III), [D-Phe(2-Me,4-Et)2]oxytocin (IV), [D-Tyr(Me)2]oxytocin (V), [D-Tyr(Et)2]oxytocin (VI) and [L-Tyr(2-Me)2]oxytocin (VII) were synthesized. All analogs with D-stereoisomer of alkyl or alkoxy substituted phenylalanine possess uterus in vitro inhibiting activity. In the case of L-stereoisomers the structure activity relationship is more complicated. As far as the pressor activity is concerned, the analogs have either very low agonistic activity or low degree of antagonism.

Synthesis of peptides by the solid-phase method. III. Bradykinin: fragments and analogs

1978 ◽  
Vol 56 (2) ◽  
pp. 92-100 ◽  
Author(s):  
W. K. Park ◽  
S. A. St-Pierre ◽  
J. Barabé ◽  
D. Regoli
Keyword(s):  
Solid Phase ◽  
Rabbit Aorta ◽  
Paper Electrophoresis ◽  
Phase Method ◽  
Biological Assays ◽  
Anaesthetized Rats ◽  
Solid Phase Method ◽  
Specific Receptors ◽  
Layer Chromatography

The natural sequence of bradykinin (BK) and 55 fragments or analogs of this peptide were prepared via the solid-phase method. The peptides were purified using ion-exchange (O-carboxymethyl (CM)) and partition (Sephadex G-25) chromatography. The purity of each peptide was established by paper and thin-layer chromatography, paper electrophoresis, amino acid analysis, and biological assays. The compounds were tested in anaesthetized rats (test in vivo) and in two smooth-muscle preparations (rabbit aorta strip, cat ileum strip) in which BK produces contraction by stimulating specific receptors of different types. Some of the new peptides are interesting in that they either resist pulmonary inactivation, or are more potent than BK itself, or antagonize the myotropic effect of BK in rabbit aorta strips.

scholarly journals Interleukin-1 Receptor Modulation Using β-Substituted α-Amino-γ-Lactam Peptides From Solid-Phase Synthesis and Diversification

2020 ◽  
Vol 8 ◽  
Author(s):  
Azade Geranurimi ◽  
Colin W. H. Cheng ◽  
Christiane Quiniou ◽  
France Côté ◽  
Xin Hou ◽  
...  
Keyword(s):  
Retinopathy Of Prematurity ◽  
Solid Phase ◽  
Interleukin 1 ◽  
Building Blocks ◽  
Phase Method ◽  
Functional Selectivity ◽  
Amino Acid Peptide ◽  
Receptor Modulation

As a key cytokine mediator of inflammation, interleukin-1β (IL-1β) binds to the IL-1 receptor (IL-1R) and activates various downstream signaling mediators, including NF-κB, which is required for immune vigilance and cellular protection. Toward the development of IL-1-targeting therapeutics which exhibit functional selectivity, the all-D-amino acid peptide 1 (101.10, H-D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH2) was conceived as an allosteric IL-1R modulator that conserves NF-κB signaling while inhibiting other IL-1-activated pathways. Employing β-hydroxy-α-amino-γ-lactam (Hgl) stereoisomers to study the conformation about the Thr3 residue in 1, [(3R,4S)-Hgl3]-1 (2b), among all possible diastereomers, was found to exhibit identical in vitro and in vivo activity as the parent peptide and superior activity to the α-amino-γ-lactam (Agl) counterpart. Noting the relevance of the β-hydroxyl substituent and configuration for the activity of (3R,4S)-2b, fifteen different β-substituted-Agl3 analogs of 1 (e.g., 2c-q) have now been synthesized by a combination of solution- and solid-phase methods employing N-Fmoc-β-substituted-Agl3-Val-OH dipeptide building blocks. Introduction of a β-azido-Agl3 residue into the resin bound peptide and subsequent reduction and CuAAC chemistry gave access to a series of amine and triazole derivatives (e.g., 2h-q). β-Substituted-[Agl3]-1 analogs 2c-q exhibited generally similar circular dichroism (CD) spectra as that of Hgl analog 2b in water, presenting curve shapes indicative of β-turn structures. The relevance of the β-substituent was indicated in rodent models of preterm labor and retinopathy of prematurity (ROP), in which certain analogs inhibited preterm birth and vaso-obliteration, respectively, with activity similar to 1 and 2b. The β-substituted-[Agl3]-1 analogs exhibited functional selectivity on IL-1-induced signaling pathways. The described solid-phase method has provided discerning probes for exploring peptide structure-activity relationships and valuable leads for developing prototypes to treat inflammatory events leading to prematurity and retinopathy of prematurity, which are leading causes of infant morbidity and blindness respectively.

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