[MeArg1, NLe10]-apelin-12: Optimization of solid-phase synthesis and evaluation of biological properties in vitro and in vivo

Peptides ◽  
2020 ◽  
Vol 129 ◽  
pp. 170320 ◽  
Author(s):  
Maria Sidorova ◽  
Irina Studneva ◽  
Valery Bushuev ◽  
Marina Pal’keeva ◽  
Alexander Molokoedov ◽  
...  
Keyword(s):  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Properties ◽  
Phase Synthesis

Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

1987 ◽  
Vol 52 (9) ◽  
pp. 2317-2325 ◽  
Author(s):  
Jan Hlaváček ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Walter Y. Chan ◽  
Victor J. Hruby
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
The Other ◽  
Amino Acid Residues ◽  
Phase Synthesis ◽  
Other Hand ◽  
Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

scholarly journals A convenient and efficient total solid-phase synthesis of DOTA-functionalized tumor-targeting peptides for PET imaging of cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Subhani M. Okarvi ◽  
Ibrahim AlJammaz
Keyword(s):  
Tumor Targeting ◽  
Chelating Agents ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Cost Effective ◽  
Binding Affinities ◽  
Phase Synthesis ◽  
Metal Chelating

Abstract Introduction An efficient and cost-effective synthesis of the metal chelating agents that couple to tumor-targeting peptides is required to enhance the process of preclinical research toward the clinical translation of molecular imaging agents. DOTA is one of the most widely used macrocyclic ligands for the development of new metal-based imaging and therapeutic agents owing to its ability to form stable and inert complexes under physiological conditions. Although solid-phase synthesis compatible DOTA-tris-(t-Bu ester) is a commercial product, it is expensive and contain chemical impurities. There is a need to explore new and cost-effective methods for the preparation of metal chelating agents, i.e., DOTA, directly on solid support to facilitate rapid, cost-effective, and high purity preparation of DOTA-linked peptides for imaging and therapy. In the present study, we describe a facile synthetic strategy of DOTA preparation and its linkage to peptides directly on solid-phase support. Methods Bombesin (BN) peptides were functionalized with DOTA chelator prepared from cyclen precursor on solid-phase and from commercial DOTA-tris and radiolabeled with 68Ga. In vitro BN/GRP receptor binding affinities of the corresponding radiolabeled peptides were determined by saturation binding assays on human breast MDA-MB-231, MCF7, T47D, and PC3 prostate cancer cells. Pharmacokinetics were studied in Balb/c mice and in vivo tumor targeting in MDA-MB-231 tumor-bearing nude mice. Results DOTA was prepared successfully from cyclen on solid-phase support, linked specifically to BN peptides and resultant DOTA-coupled peptides were radiolabeled efficiently with 68Ga. The binding affinities of all the six BN peptides were comparable and in the low nanomolar range. All 68Ga-labeled peptides showed high metabolic stability in plasma. These radiopeptides exhibited rapid pharmacokinetics in Balb/c mice with excretion mainly through the urinary system. In nude mice, MDA-MB-231 tumor uptake profiles were slightly different; the BN peptide with Ahx spacer and linked to DOTA through cyclen exhibited higher tumor uptake (2.32% ID/g at 1 h post-injection) than other radiolabeled BN peptides investigated in this study. The same leading BN peptide also displayed favorable pharmacokinetic profile in Balb/c mice. The PET images clearly visualized the MDA-MB-231 tumor. Conclusions DOTA prepared from cyclen on solid-phase support showed comparable potency and efficiency to DOTA-tris in both in vitro and in vivo evaluation. The synthetic methodology described here allows versatile, site-specific introduction of DOTA into peptides to facilitate the development of DOTA-linked molecular imaging and therapy agents for clinical translation.

Solid phase synthesis and biological activities of oxytocin carba analogues containing threonine in position 4

1985 ◽  
Vol 50 (2) ◽  
pp. 418-427 ◽  
Author(s):  
Michal Lebl ◽  
Victor J. Hruby ◽  
Jiřina Slaninová ◽  
Tomislav Barth
Keyword(s):  
Biological Activity ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Activities ◽  
High Biological Activity ◽  
Phase Synthesis

Solis phase methodology was developed for the synthesis of carba-analogues of oxytocin. Two known compounds (deamino-1-carba-oxytocin (I) and deamino-6-carba-oxytocin (II)) and two new analogues ([4-threonine]deamino-1-carba-oxytocin (III) and [4-threonine]deamino-6-carba-oxytocin (IV)) were synthesized using different approaches. The latter two compounds were found to possess high biological activity in the rat uterotonic (in vitro and in vivo) and galactogogic (in vivo) assays.

Solid Phase Synthesis of Novel Fullerene Nucleotides Conjugates

2011 ◽  
Vol 266 ◽  
pp. 200-203
Author(s):  
Jing Zhang ◽  
Ya Dong Zhang
Keyword(s):  
Aspartic Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Properties ◽  
Azomethine Ylide ◽  
Hydroxyl Group ◽  
Spectrometric Analysis ◽  
Phase Synthesis ◽  
Chemical Structures ◽  
Controlled Pore Glass

N-substituted 3, 4-fullero pyrrolidine was synthesized according to 1, 3-dipolar cycloaddition of the azomethine ylide. Aspartic acid with protected α-amino and α-carboxyl groups was reacted with the activated hydroxyl group of N-substituted 3, 4-fullero pyrrolidine. The products were deprotected, affording the monofullerene aspartic acid (mFas). The conjugate FasT was synthesized by reaction of mFas containing protected amino group with the thymidylic acid derivatived controlled pore glass (CPG) using solid phase synthesis. All of the above fullerene derivatives were characterized by UV–vis, 1H NMR, IR and MS spectrometric analysis, giving the correct spectra with regard to their chemical structure. The chemical structures of fullerene nucleotides conjugate FasT is different from previous reports and may have novel biological properties. Moreover, they are more suitable for applications in biomedical research due to their solubilization in THF and DMSO. They have a potential to be used as monomer for the automatic synthesis. It allows further conjugation with specific biomolecules including amino acids, peptides, nucleotides and nucleic acids. A novel method has been developed to synthesize fullerene nucleotides conjugate. Their unique chemical structures make them very interesting for their potential use in medicine and biology.

A convenient solid-phase synthesis methodology for preparing peptide-derived molecular imaging agents — Synthesis, characterization, and in vitro screening of Tc(I) – chemotactic peptide conjugates

2005 ◽  
Vol 83 (12) ◽  
pp. 2060-2066 ◽  
Author(s):  
Karin A Stephenson ◽  
Sangeeta Ray Banerjee ◽  
Nicole McFarlane ◽  
Douglas R Boreham ◽  
Kevin P Maresca ◽  
...  
Keyword(s):  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Metal Chelate ◽  
Free Ligand ◽  
Peptide Sequence ◽  
In Vitro Screening ◽  
Chemotactic Peptide ◽  
Phase Synthesis ◽  
Synthesis Strategy

A versatile solid-phase synthesis strategy for preparing peptide–chelate conjugates was developed. The methodology was optimized using a series of ligands, designed to bind Tc(I)/Re(I), and a chemotactic peptide fMFL, which was exploited as a model targeting vector. The peptide derivatives were prepared in parallel using a conventional automated peptide synthesizer in multi-milligram quantities, which provided sufficient material to perform complete characterization, radiolabelling, and in vitro screening studies. Because of the robust nature of the metal–chelate complexes, the Re complex of a chelate–peptide conjugate was prepared on the resin using the same methodology employed to prepare the free ligand conjugates. As such, the reported methodology is amenable to the preparation of libraries of novel Tc radiopharmaceutical ligands and their corresponding Re reference standards in which several factors, including peptide sequence, site of derivatization, and both the type and length of the spacer, can be easily varied.Key words: radiopharmaceuticals, technetium, rhenium, peptides, solid-phase synthesis.

Solid-phase synthesis and in vitro biological activity of a Thr4→Ser4 analog of daptomycin

2015 ◽  
Vol 25 (23) ◽  
pp. 5490-5494 ◽  
Author(s):  
Chuda Raj Lohani ◽  
Robert Taylor ◽  
Michael Palmer ◽  
Scott D. Taylor
Keyword(s):  
Biological Activity ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Phase Synthesis

Synthesis and biological properties of vasopressin analogues containing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

1990 ◽  
Vol 55 (4) ◽  
pp. 1099-1105 ◽  
Author(s):  
Zdenko Procházka ◽  
Juris E. Ancans ◽  
Jiřina Slaninová ◽  
Alena Machová ◽  
Tomislav Barth ◽  
...  
Keyword(s):  
Amino Acid ◽  
Carboxylic Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Activities ◽  
Biological Properties ◽  
Phase Synthesis ◽  
Aromatic Residues ◽  
Synthesis Methodology ◽  
Vasopressin Analogues

Solid phase synthesis methodology on a benzhydrylamine resin was used for the synthesis of three analogues of vasopressin with the non-coded amino acid, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), in the position 2 ([Tic2, Lys8]VP (I)) and in the position 3 ([Tic3, Lys8]VP (II)). The analogue containing only one Tic in place of both aromatic residues was also isolated (des-Tyr2-[Tic3, Lys8]VP (III)). The biological activities of all analogues were negligible.

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