99896-85-2

Basic information

• Product Name: ARG-GLY-ASP
• Synonyms: H2N-RGD-OH;H-ARG-GLY-ASP-OH;L-ARG-GLY-ASP;ARGINYL-GLYCYL-ASPARTIC ACID;ARG-GLY-ASP;ARG-GLY-ASP PEPTIDE;Arg-Gly-Asp acetate;Arginyl-glycyl-asparagilin
• CAS NO: 99896-85-2
• Molecular Formula: C₁₂H₂₂N₆O₆
• Molecular Weight: 346.34
• Product Categories: Peptide;Cell Signaling Enzymes;ECM ProteinsCytoskeleton and Extracellular Matrix;Extracellular Matrix;Extracellular Matrix Peptides (ECM);Extracellular Matrix Peptides and ProteinsPeptides for Cell Biology;Fibronectin Fragments and Analogs;Matrix Metalloproteinases Products;Various Peptides
• Mol File: 99896-85-2.mol
• Article Data: 5

Chemical Properties

• Melting Point: 153-155℃ (ethyl ether )
• Boiling Point: 597.205°C at 760 mmHg
• Flash Point: 314.979°C
• Appearance: /
• Density: 1.61 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.671
• Storage Temp.: −20°C
• Solubility: Soluble in 0.1N acetic acid at 20mg/ml
• PKA: 2.85±0.10(Predicted)
• CAS DataBase Reference: ARG-GLY-ASP(CAS DataBase Reference)
• NIST Chemistry Reference: ARG-GLY-ASP(99896-85-2)
• EPA Substance Registry System: ARG-GLY-ASP(99896-85-2)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 99896-85-2(Hazardous Substances Data)

Usage

Chemical Properties

White to off-white powder

Uses

Arg-Gly-Asp has been used:to saturate the cell surface Arg-Gly-Asp (RGD) receptors and inhibit marrow stromal cell (MSC) attachment to peptide modified hydrogelin adhesion assayin inhibition assay to confirm the β1-integrin-dependency of cell adhesionin textile fabrication and RGD textile functionalizationto engineer a population of human dermal fibroblasts with impaired migrationto modify glass substrate and evaluate the behavior of human bone marrow mesenchymal stem cells (hBM-MSCs)in the cell culture of human mammary epithelial cells

General Description

Arg-Gly-Asp (RGD) is an integrin binding site, which belongs to the class of adhesive proteins. It functions as a brain tumor targeting ligand.

Biological Activity

synthetic peptides containing the arginine-glycine-aspartate (rgd) were extensively used as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth and differentiation, since the rgd motif is an integrin-recognition motif found in many ligands.

Biochem/physiol Actions

Primary sequence involved with the binding of proteins to cell surfaces

in vitro

rgd peptide can induce apoptosis in the absence of signals and integrin-mediated cell clustering. previous study demonstrates that rgd peptides promote apoptosis through activation of conformation changes enhancing pro-caspase-3 activation and autoprocessing [1].

in vivo

anima study suggested that the rgd-4c-fitc-peptide bound to both endothelial and tumor cells in vivo and that peptide targeting should allow the delivery of therapeutic drugs to both endothelial and tumor cells [2].

references

[1] nature. 1999 feb 11;397(6719):534-9.rgd peptides induce apoptosis by direct caspase-3 activation. buckley cd1, pilling d, henriquez nv, parsonage g, threlfall k, scheel-toellner d, simmons dl, akbar an, lord jm, salmon m. [2] cancer res. 2002 sep 15;62(18):5139-43. arginine-glycine-aspartic acid (rgd)-peptide binds to both tumor and tumor-endothelial cells in vivo. zitzmann s1, ehemann v, schwab m.

InChI:InChI=1/C12H22N6O6/c13-4-6(19)12(17,10(23)24)7(9(21)22)8(20)5(14)2-1-3-18-11(15)16/h5,7H,1-4,13-14,17H2,(H,21,22)(H,23,24)(H4,15,16,18)

Synthetic route

Arg(Pbf)-Gly-Asp(OtBu) → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
With methanol; triethylsilane; water; trifluoroacetic acid at 20℃; for 2h;	72%

glycyl-L-aspartic acid (4685-12-5) + Nα,NG,NG'-tri-Boc-L-arginine N-hydroxysuccinimide ester (108787-79-7) → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
Stage #1: glycyl-L-aspartic acid; Nα,NG,NG'-tri-Boc-L-arginine N-hydroxysuccinimide ester With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; for 24h; Addition; Stage #2: With trifluoroacetic acid In chloroform Hydrolysis; deprotection;	54%

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-(tBu)Asp-OH (71989-14-5) + N-α-Fmoc-N-γ-(2,2,5,7,8-pentamethylchroman-6-sulfonyl)-L-arginine → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
Multistep reaction;

Z-Gly-Asp(OBu)-OH (131668-52-5) → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 4-toluenesulfonic acid; H2 / Pd/C / dimethylformamide / 48 h 2.1: N-methylmorpholine / dimethylformamide / 24 h / 20 °C 2.2: 54 percent / TFA, 50 percent / CHCl3 View Scheme

p-cresol (106-44-5) + thiophenol (108-98-5) → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
In hydrogen fluoride

N-Fmoc-β-alanine (35737-10-1) + Arg-Gly-Asp (99896-85-2) + β-Alanine pNb ester hydrochloride + N-α-Fmoc-N-β-alloc-L-diaminopropionic acid (188970-92-5) → c[L-Dapa(RGD)-βAla-L-Dapa(RGD)-βAla]

Conditions	Yield
Multistep reaction;	100%

α-acryloyl-ω-N-succinimidyl-acetate-PEG + Arg-Gly-Asp (99896-85-2) → Ac-PEG-RGD

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 17h; Product distribution / selectivity; Sonographic reaction;	59%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 1h; Product distribution / selectivity;

1,2-dioleyol-sn-glycero-3-phosphoethanolamine-n-[poly(ethyleneglycol)]-N-benzotriazole carbonate, PEG MW = 3400 + Arg-Gly-Asp (99896-85-2) → 1,2-dioleyol-sn-glycero-3-phosphoethanolamine-n-[poly(ethyleneglycol)]-N-benzotriazole carbonate : Arg-Gly-Asp conjugate, 2:1 molar ratio, PEG MW = 3400

Conditions	Yield
In various solvent(s) at 4℃; for 4h; pH=7.5;

α-hydroxy-ω-N-succinimidyl-acetate-PEG + Arg-Gly-Asp (99896-85-2) → HO-PEG-RGD

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 19h;

Arg(Pbf)-Gly-Asp(OtBu) → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
With methanol; triethylsilane; water; trifluoroacetic acid at 20℃; for 2h;	72%

glycyl-L-aspartic acid (4685-12-5) + Nα,NG,NG'-tri-Boc-L-arginine N-hydroxysuccinimide ester (108787-79-7) → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
Stage #1: glycyl-L-aspartic acid; Nα,NG,NG'-tri-Boc-L-arginine N-hydroxysuccinimide ester With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃; for 24h; Addition; Stage #2: With trifluoroacetic acid In chloroform Hydrolysis; deprotection;	54%

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-(tBu)Asp-OH (71989-14-5) + N-α-Fmoc-N-γ-(2,2,5,7,8-pentamethylchroman-6-sulfonyl)-L-arginine → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
Multistep reaction;

Z-Gly-Asp(OBu)-OH (131668-52-5) → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 4-toluenesulfonic acid; H2 / Pd/C / dimethylformamide / 48 h 2.1: N-methylmorpholine / dimethylformamide / 24 h / 20 °C 2.2: 54 percent / TFA, 50 percent / CHCl3 View Scheme

p-cresol (106-44-5) + thiophenol (108-98-5) → Arg-Gly-Asp (99896-85-2)

Conditions	Yield
In hydrogen fluoride

N-Fmoc-β-alanine (35737-10-1) + Arg-Gly-Asp (99896-85-2) + β-Alanine pNb ester hydrochloride + N-α-Fmoc-N-β-alloc-L-diaminopropionic acid (188970-92-5) → c[L-Dapa(RGD)-βAla-L-Dapa(RGD)-βAla]

Conditions	Yield
Multistep reaction;	100%

α-acryloyl-ω-N-succinimidyl-acetate-PEG + Arg-Gly-Asp (99896-85-2) → Ac-PEG-RGD

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 17h; Product distribution / selectivity; Sonographic reaction;	59%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 1h; Product distribution / selectivity;

1-(vinylsulfonyl)-4-fluorobenzene (28122-14-7) + Arg-Gly-Asp (99896-85-2) → C20H29FN6O8S

Conditions	Yield
In methanol at 50℃; pH=8.5;	55%

1,2-dioleyol-sn-glycero-3-phosphoethanolamine-n-[poly(ethyleneglycol)]-N-benzotriazole carbonate, PEG MW = 3400 + Arg-Gly-Asp (99896-85-2) → 1,2-dioleyol-sn-glycero-3-phosphoethanolamine-n-[poly(ethyleneglycol)]-N-benzotriazole carbonate : Arg-Gly-Asp conjugate, 2:1 molar ratio, PEG MW = 3400

Conditions	Yield
In various solvent(s) at 4℃; for 4h; pH=7.5;

α-hydroxy-ω-N-succinimidyl-acetate-PEG + Arg-Gly-Asp (99896-85-2) → HO-PEG-RGD

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 19h;

Arg-Gly-Asp (99896-85-2) + collagen → arginine-glycine-aspartic acid peptide modified 3D collagen matrix

Conditions	Yield
With 1,2-dichloro-ethane In water at 37℃; for 18h;

isoleucinyllysinylvalylalanylvaline + Arg-Gly-Asp (99896-85-2) + collagen → arginine-glycine-aspartic acid-isoleucine-lysine-valine-alanine-valine peptides modified 3D collagen matrix

Conditions	Yield
With 1-hydroxy-pyrrolidine-2,5-dione; 1,2-dichloro-ethane In water at 37℃; for 18h;

Arg-Gly-Asp (99896-85-2) → L-malic acid (2174-58-5) + L-arginine (74-79-3) + glycine (56-40-6)

Conditions	Yield
With hydrogenchloride In water for 24h; Reflux;

Arg-Gly-Asp (99896-85-2) → α-D-L-arginine (127290-62-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 24 h / Reflux 2: deuterium / water-d2 / 36 h / 55 °C / 1500.15 Torr / Inert atmosphere View Scheme

Arg-Gly-Asp (99896-85-2) → Arg-Gly-Asp

Conditions	Yield
With deuterium In water-d2 at 55℃; under 1500.15 Torr; for 36h; Inert atmosphere; enantiospecific reaction;

C8H13N3O4S + Arg-Gly-Asp (99896-85-2) → C20H33N9O10

Conditions	Yield
With hydrogenchloride; sodium hydroxide; potassium hexacyanoferrate(III) In water; water-d2 at 20℃; for 0.333333h; pH=9;	76 %Spectr.

[18F]-1-fluoro-4-(vinylsulfonyl)benzene + Arg-Gly-Asp (99896-85-2) → C20H29(18)FN6O8S

Conditions	Yield
In methanol at 35℃; for 0.5h;

Upstream product

• 4685-12-5 glycyl-L-aspartic acid 
• 108787-79-7 N^α,N^G,N^G'-tri-Boc-L-arginine N-hydroxysuccinimide ester 
• 106-44-5 p-cresol 
• 108-98-5 thiophenol 
• 131668-52-5 Z-Gly-Asp(OBu)-OH 
• 29022-11-5 N-(fluoren-9-ylmethoxycarbonyl)glycine 
• 71989-14-5 Fmoc-(tBu)Asp-OH 

Downstream Products

• 2174-58-5 L-malic acid 
• 74-79-3 L-arginine 
• 56-40-6 glycine 

Relevant articles and documents

Synthesis of Modified RGD-Based Peptides and Their in vitro Activity

Arg-Gly-Asp (RGD) peptides represent the most outstanding recognition motif involved in cell adhesion that binds to the αvβ3 integrin, which has been targeted for cancer therapy. Various RGD-containing peptides and peptidomimetics have been designed and synthesized to selectively inhibit this integrin. In this study, the synthesis of RGD-based peptides through the incorporation of the short bioactive peptide Phe-Ala-Lys-Leu-Phe (FAKLF) at the C and N termini of RGD has been achieved by using a solid-phase peptide synthesis approach. The peptides were purified by means of preparative RP-HPLC and their structures were confirmed through HRMS (ESI). The MTT assay revealed that the RGD and FAKLF peptides inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, with IC50 values of 3000 and 500 ng mL?1, respectively. Interestingly, a drastic improvement was observed in the antiproliferative activity of the combined structures of the FAKLFRGD and RGDFAKLF peptides, leading to IC50 values of 200 and 136.7 ng mL?1, respectively. Meanwhile, based on apoptosis results, the potential of peptides to induce apoptosis, in accordance with their antiproliferative activity, indicated that the RGD and FAKLF peptides, and the peptides synthesized based on their combinations induced cell apoptosis in a dose-dependent manner followed by inhibition of the proliferation of endothelial cells. Moreover, the incorporation of d-leucine increased the induction of apoptosis by these peptides.

Preparation and biological activities of a bivalent poly(ethylene glycol) hybrid containing an active site and its synergistic site of fibronectin.

A bivalent poly(ethylene glycol) or PEG hybrid of fibronectin-related peptides was prepared. An active site peptide (RGD) and its synergistic site peptide (PHSRN) of fibronectin were conjugated with an amino acid-type PEG (aaPEG) to form PHSRN-aaPEG-RGD.

Tripeptides useful as immunostimulants as well as in the prevention of metastases

The present invention is referred to tripeptides having the following general formula: where X=L-Arg or D-Arg and Y=L-Asp or D-Asp. These tripeptides, endowed with both immunostimulant and antimetastatic properties, are active not only after parenteral administration, but also after oral treatment. The invention is also related to the procedure for the preparation of said compounds.