545376-68-9

Basic information

• Product Name: cyclized H₂N-Asp(OtBu)-D-Phe-Lys(Boc)-Arg(Pbf)-Gly-OH
• Synonyms: cyclized H₂N-Asp(OtBu)-D-Phe-Lys(Boc)-Arg(Pbf)-Gly-OH
• CAS NO: 545376-68-9
• Molecular Weight: 1012.24
• Mol File: 545376-68-9.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: cyclized H₂N-Asp(OtBu)-D-Phe-Lys(Boc)-Arg(Pbf)-Gly-OH(CAS DataBase Reference)
• NIST Chemistry Reference: cyclized H₂N-Asp(OtBu)-D-Phe-Lys(Boc)-Arg(Pbf)-Gly-OH(545376-68-9)
• EPA Substance Registry System: cyclized H₂N-Asp(OtBu)-D-Phe-Lys(Boc)-Arg(Pbf)-Gly-OH(545376-68-9)

Safety Data

• Hazardous Substances Data: 545376-68-9(Hazardous Substances Data)

Upstream product

• 187618-60-6 Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine 
• 71989-26-9 Fmoc-Lys(tert-butoxycarbonyl) 
• 71989-14-5 Fmoc-(tBu)Asp-OH 

Downstream Products

• 161552-03-0 [(2S,5R,8S,11S)-8-(4-Amino-butyl)-5-benzyl-11-(3-guanidino-propyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaaza-cyclopentadec-2-yl]-acetic acid 

Relevant articles and documents

Synthesis and Biological Evaluation of Paclitaxel Conjugates Involving Linkers Cleavable by Lysosomal Enzymes and αVβ3-Integrin Ligands for Tumor Targeting

Two cyclo[DKP-RGD]-PTX (PTX = paclitaxel) and two cyclo[RGDfK]-PTX conjugates containing the Gly-Phe-Leu-Gly (GFLG) linker, which is cleavable by lysosomal enzymes, were synthesized and compared to two cyclo[DKP-RGD]-Val-Ala-PTX conjugates. The conjugates were evaluated for their ability to inhibit biotinylated vitronectin binding to the isolated αvβ3 receptor, retaining good binding affinity, in the same nanomolar range of the free ligands. Cell viability assays were performed for the six conjugates in the αvβ3+ U87 and in the αvβ3– HT29 cell lines. Loss of potency was observed for all the conjugates, attenuated by the presence of a tetraethylene glycol (PEG-4) spacer. A good Targeting Index (TI = Relative Potency in the αvβ3+ U87/Relative Potency in the αvβ3– HT29) was displayed by the conjugates, in particular by cyclo[DKP-RGD]-PEG-4-Val-Ala-PTX 9 (TI = 533). This conjugate was tested in the αvβ3+ U87 cell line in the presence of 50-fold excess free cyclo[DKP-RGD] ligand 2. In this competition experiment, a fivefold decrease of the conjugate cytotoxicity was calculated, suggesting that the conjugate is possibly internalized by an αvβ3 integrin-mediated process.

Synthesis of DOTA-conjugated multivalent cyclic-RGD peptide dendrimers via 1,3-dipolar cycloaddition and their biological evaluation: Implications for tumor targeting and tumor imaging purposes

This report describes the design and synthesis of a series of αVβ3 integrin-directed monomeric, dimeric and tetrameric cyclo[Arg-Gly-Asp-d-Phe-Lys] dendrimers using "click chemistry". It was found that the unprotected N-ε-azido derivative of cyclo[Arg-Gly-Asp-d-Phe-Lys] underwent a highly chemoselective conjugation to amino acid-based dendrimers bearing terminal alkynes using a microwave-assisted Cu(i)-catalyzed 1,3-dipolar cycloaddition. The αVβ 3 binding characteristics of the dendrimers were determined in vitro and their in vivo αVβ3 targeting properties were assessed in nude mice with subcutaneously growing human SK-RC-52 tumors. The multivalent RGD-dendrimers were found to have enhanced affinity toward the αVβ3 integrin receptor as compared to the monomeric derivative as determined in an in vitro binding assay. In case of the DOTA-conjugated 111In-labeled RGD-dendrimers, it was found that the radiolabeled multimeric dendrimers showed specifically enhanced uptake in αVβ3 integrin expressing tumors in vivo. These studies showed that the tetrameric RGD-dendrimer had better tumor targeting properties than its dimeric and monomeric congeners. This journal is The Royal Society of Chemistry.