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

[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.

Download Full-text

Comparison of the Potency of 8-L-Arginine, 8-D-Arginine and 8-D-Homoarginine Vasopressin Analogs with Substituted Phenylalanine in Position 2

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19941439 ◽

1994 ◽

Vol 59 (6) ◽

pp. 1439-1450 ◽

Cited By ~ 2

Author(s):

Miroslava Žertová ◽

Jiřina Slaninová ◽

Zdenko Procházka

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Basic Amino Acid ◽

The Other ◽

Side Chain ◽

Inhibitory Potency ◽

Phase Synthesis ◽

Other Hand ◽

Order Of Magnitude

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.

Download Full-text

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

Peptides ◽

10.1016/j.peptides.2020.170320 ◽

2020 ◽

Vol 129 ◽

pp. 170320 ◽

Cited By ~ 1

Author(s):

Maria Sidorova ◽

Irina Studneva ◽

Valery Bushuev ◽

Marina Pal’keeva ◽

Alexander Molokoedov ◽

...

Keyword(s):

Solid Phase Synthesis ◽

Solid Phase ◽

Biological Properties ◽

Phase Synthesis

Download Full-text

A New Strategy for the Preparation of Peptide-Targeted Radiopharmaceuticals Based on an Fmoc-Lysine-Derived Single Amino Acid Chelate (SAAC). Automated Solid-Phase Synthesis, NMR Characterization, and in Vitro Screening of fMLF(SAAC)G and fMLF[(SAAC−Re(CO)3)+]G

Bioconjugate Chemistry ◽

10.1021/bc034128s ◽

2004 ◽

Vol 15 (1) ◽

pp. 128-136 ◽

Cited By ~ 81

Author(s):

Karin A. Stephenson ◽

Jon Zubieta ◽

Sangeeta Ray Banerjee ◽

Murali K. Levadala ◽

Linda Taggart ◽

...

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Single Amino Acid ◽

In Vitro Screening ◽

Phase Synthesis ◽

Nmr Characterization ◽

New Strategy ◽

Acid Chelate

Download Full-text

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

EJNMMI Research ◽

10.1186/s13550-019-0539-0 ◽

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.

Download Full-text

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

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19850418 ◽

1985 ◽

Vol 50 (2) ◽

pp. 418-427 ◽

Cited By ~ 8

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.

Download Full-text

Synthesis of Fragments of the Vasoactive Intestinal Peptide (VIP) and Analysis of Their Residual Biological Activities

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19951229 ◽

1995 ◽

Vol 60 (7) ◽

pp. 1229-1235 ◽

Cited By ~ 2

Author(s):

Ivana Zoulíková ◽

Ivan Svoboda ◽

Jiří Velek ◽

Václav Kašička ◽

Jiřina Slaninová ◽

...

Keyword(s):

Amino Acid ◽

Biological Activities ◽

Residual Activity ◽

Detailed Examination ◽

Amino Acid Residues ◽

Linear Peptide ◽

Zone Electrophoresis ◽

Capillary Zone

The vasoactive intestinal (poly)peptide (VIP) is a linear peptide containing 28 amino acid residues, whose primary structure indicates a low metabolic stability. The following VIP fragments, as potential metabolites, and their analogues were prepared by synthesis on a solid: [His(Dnp)1]VIP(1-10), VIP(11-14), [D-Arg12]VIP(11-14), [Lys(Pac)15,21,Arg20]VIP(15-22), and VIP(23-28). After purification, the peptides were characterized by amino acid analysis, mass spectrometry, RP HPLC, and capillary zone electrophoresis. In some tests, detailed examination of the biological activity of the substances in vivo and in vitro gave evidence of a low, residual activity of some fragments, viz. a depressoric activity in vivo for [His(Dnp)1]VIP(1-10) and a stimulating activity for the release of α-amylase in vitro and in vivo for [Lys(Pac)15,21,Arg20]VIP(15-22) and VIP(23-28).

Download Full-text

In vitro insulin-mimetic activity and in vivo metallokinetic feature of oxovanadium(IV)porphyrin complexes in healthy rats

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424612004458 ◽

2012 ◽

Vol 16 (01) ◽

pp. 114-121 ◽

Cited By ~ 2

Author(s):

Tapan K. Saha ◽

Yutaka Yoshikawa ◽

Hirouki Yasui ◽

Hiromu Sakurai

Keyword(s):

The Other ◽

Insulin Mimetic ◽

Other Hand ◽

Better Than

We prepared [meso-tetrakis(4-carboxylatophenyl)porphyrinato]oxovanadium(IV) tetrasodium, ([VO(tcpp)]Na4), and investigated its in vitro insulin-mimetic activity and in vivo metallokinetic feature in healthy rats. The results were compared with those of previously proposed insulin-mimetic oxovanadium(IV)porphyrin complexes and oxovanadium(IV) sulphate. The in vitro insulin-mimetic activity and bioavailability of [VO(tcpp)]Na4 were considerably better than those of [meso-tetrakis (1-methylpyridinium-4-yl)porphyrinato]oxovanadium(IV)(4+) tetraperchlorate ([VO(tmpyp)](ClO4)4) and oxovanadium(IV) sulphate. On the other hand, [VO(tcpp)]Na4 and [meso-tetrakis(4-sulfonatophenyl) porphyrinato]oxidovanadate(IV)(4-)([VO(tpps)]) showed very similar in vitro insulin-mimetic activity and in vivo metallokinetic feature in healthy rats. In particular, the order of in vitro insulin-mimetic activity of the complexes was determined to be: [VO(tcpp)]Na4 ≈ [VO(tpps)] > ([VO(tmpyp)](ClO4)4 > oxovanadium(IV) sulphate.

Download Full-text