704-15-4

Basic information

• Product Name: GLYCYL-L-PROLINE
• Synonyms: 1-(Aminoacetyl)proline;Glycylproline;L-Proline, 1-glycyl-;N-Glycyl-L-proline;Proline, 1-glycyl-, L-;H-GLY-PRO-OH;GLYCYL-L-PROLINE;GLY-PRO
• CAS NO: 704-15-4
• Molecular Formula: C₇H₁₂N₂O₃
• Molecular Weight: 172.18
• EINECS: 211-880-2
• Product Categories: PYRROLE;Biochemistry;Oligopeptides;Peptide Synthesis;Dipeptides;Dipeptides and Tripeptides;Peptides
• Mol File: 704-15-4.mol
• Article Data: 15

Chemical Properties

• Melting Point: 185℃
• Boiling Point: 411.3 °C at 760 mmHg
• Flash Point: 202.6 °C
• Appearance: /
• Density: 1.356 g/cm³
• Vapor Pressure: 6.44E-08mmHg at 25°C
• Refractive Index: -114 ° (C=4, H2O)
• Storage Temp.: −20°C
• Solubility: Water (Slightly)
• PKA: 3.18±0.20(Predicted)
• Water Solubility: very faint turbidity
• CAS DataBase Reference: GLYCYL-L-PROLINE(CAS DataBase Reference)
• NIST Chemistry Reference: GLYCYL-L-PROLINE(704-15-4)
• EPA Substance Registry System: GLYCYL-L-PROLINE(704-15-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 704-15-4(Hazardous Substances Data)

Usage

Chemical Properties

Crystalline

Uses

Different sources of media describe the Uses of 704-15-4 differently. You can refer to the following data:
1. N-Glycylproline was found to exhibit anti-ischemic effects on the metabolism of neuroactive amino acids and indices of energy turnover in the neocortex of rats after experimental brain ischemia.
2. Substrate for Prolidase.

Definition

ChEBI: A dipeptide consisting of L-proline having a glycyl residue attached to its alpha-amino group.

Purification Methods

Crystallise glycyl-L-proline from water at 50-60o by addition of EtOH. [Saidel J Am Chem Soc 77 3893 1955, Bergmann et al. Z Physiol Chem 212 79 1932, Beilstein 22 IV 49.]

InChI:InChI=1/C7H12N2O3/c8-4-6(10)9-3-1-2-5(9)7(11)12/h5H,1-4,8H2,(H,11,12)/t5-/m0/s1

Synthetic route

(S)-1-(2-chloroacetyl)pyrrolidine-2-carboxylic acid (23500-10-9) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With ammonium hydroxide

(2S)-1-(2-[[(benzyloxy)carbonyl]amino]acetyl)tetrahydro-1H-pyrrole-2-carboxylic acid (1160-54-9) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With methanol; palladium; acetic acid Hydrogenation;
With hydrogen; palladium on activated charcoal

1-(bromoacetyl)-L-proline (95688-74-7) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With ammonium hydroxide

1-iodoacetyl-L-proline → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With ammonium hydroxide

L-alanin (56-41-7) + H-Gly-Pro-pNA (60189-43-7) → 4-nitro-aniline (100-01-6) + gly-pro-ala (837-83-2) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With dipeptidyl peptidase IV In glycerol at 40℃;
With dipeptidyl peptidase IV In glycerol at 40℃; Rate constant; Kinetics; constant of partition;

L-tyrosine (60-18-4) + H-Gly-Pro-pNA (60189-43-7) → Gly-Pro-Tyr (22028-91-7) + 4-nitro-aniline (100-01-6) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With dipeptidyl peptidase IV In glycerol at 40℃;
With dipeptidyl peptidase IV In glycerol at 40℃; Rate constant; Kinetics; constant of partition;

gly-pro-ala (837-83-2) → L-alanin (56-41-7) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
at 37℃; for 0.166667h; 0.1 M Tris HCl buffer pH 8.0, X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris nTR;
at 37℃; for 0.166667h; Rate constant; 0.1 M Tris HCl buffer pH 8.0, X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris nTR; Km;

H-Gly-Pro-pNA (60189-43-7) → 4-nitro-aniline (100-01-6) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
at 37℃; for 0.166667h; 0.1 M Tris HCl buffer pH 8.0, X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris nTR;
With buffer pH=7.6; dipeptidyl peptidase IV In glycerol at 30℃; Rate constant; Kinetics;
at 37℃; for 0.166667h; Rate constant; 0.1 M Tris HCl buffer pH 8.0, X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris nTR; Km, Ki, competitive inhibition by dipeptides;

L-tyrosyl-L-prolyl-L-phenylalanyl-L-prolyl-glycyl-L-prolyl-L-isoleucine (72122-62-4) → H-Tyr-Pro-OH (51871-47-7) + L-phenylalanyl-L-proline (7669-65-0) + Gly-Pro-Ile (89187-15-5) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
at 37℃; for 7h; 0.1 M Tris HCl buffer pH 8.0, X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris nTR; Yield given. Yields of byproduct given;

L-tyrosyl-L-prolyl-L-phenylalanyl-L-prolyl-glycyl-L-prolyl-L-isoleucine (72122-62-4) → H-Tyr-Pro-OH (51871-47-7) + L-phenylalanyl-L-proline (7669-65-0) + Gly-Pro-Ile (89187-15-5) + Phe-Pro-Gly-Pro-Ile + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
at 37℃; Kinetics; 0.1 M Tris HCl buffer pH 8.0, X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis subsp. cremoris nTR;

Z-Gly-Pro-Leu-Gly-Pro (2646-61-9) → N-[1-(N-benzyloxycarbonyl-glycyl)-L-prolyl]-L-leucine (2646-63-1) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With alkaline proteinase S; tris hydrochloride In water at 37℃; for 0.166667h; hydrolysis rate;

(S)-1-(2-Carboxyamino-acetyl)-pyrrolidine-2-carboxylic acid → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With borax; sodium dihydrogenphosphate at 26℃; Equilibrium constant;

H-Gly-Pro-pNA (60189-43-7) + glycine (56-40-6) → 4-nitro-aniline (100-01-6) + H-Gly-Pro-OH (704-15-4) + Gly-Pro-Gly (2441-63-6)

Conditions	Yield
With dipeptidyl petidase IV In glycerol at 40℃;
With dipeptidyl peptidase IV In glycerol at 40℃; Rate constant; Kinetics; constant of partition;

H-Gly-Pro-pNA (60189-43-7) + L-proline (147-85-3) → Gly-Pro-Pro (13100-15-7) + 4-nitro-aniline (100-01-6) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With dipeptidyl peptidase IV In glycerol at 40℃;
With dipeptidyl peptidase IV In glycerol at 40℃; Rate constant; Kinetics; constant of partition;

(S)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione (3705-27-9) → H-Gly-Pro-OH (704-15-4) + L-prolyl-glycine

Conditions	Yield
With sodium hydroxide

glycyl-prolyl-4-methoxy-β-naphthylamide → 4-methoxy-2-naphthylamine (2764-95-6) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With dipeptidyl peptidase IV at 40℃; Product distribution;

5-glycylprolylglycyclprolyl-9-di(3-sulfonylpropyl)aminobenza[a]phenoxazolium perchlorate → (5-amino-benzo[a]phenoxazin-9-ylidene)-bis-(3-sulfo-propyl)-ammonium; perchlorate + (S)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione (3705-27-9) + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With dipeptidyl peptidase IV; HEPES buffer at 37℃; pH=7.4; Enzyme kinetics;

L-proline (147-85-3) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / caustic soda / dioxane / 24 h 2: H2 / Pd-C View Scheme
Multi-step reaction with 2 steps 1: aqueous NaOH 2: aqueous NH3 View Scheme
Multi-step reaction with 2 steps 1: aqueous NaOH 2: aqueous NH3 View Scheme

H-Pro-Gly-OMe (33256-35-8) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 110 °C / 0 Torr 2: aqueous NaOH View Scheme

glycine (56-40-6) + L-proline (147-85-3) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With recombinant His-tagged Treponema denticola ATCC35405 L-amino acid α-ligase; water; tris hydrochloride; magnesium sulfate; ATP at 37℃; for 16h; pH=8; aq. buffer; Enzymatic reaction;

N-(9H-fluoren-9-ylmethoxycarbonyl)glycyl-L-proline (212651-48-4) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With piperidine In N,N-dimethyl-formamide for 0.5h;

7-glycyl-L-prolylamino-4-methylcoumarin → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With ethylenediaminetetraacetic acid; dipeptydyl-peptidase DPP4; sodium chloride In aq. phosphate buffer at 37℃; for 0.5h; pH=7.5; Catalytic behavior; pH-value; Enzymatic reaction;

t-butyloxycarbonyl-glycyl-proline methyl ester (41863-49-4) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium hydroxide monohydrate; water / tetrahydrofuran / 0 °C 2: trifluoroacetic acid / dichloromethane / 0 °C / Inert atmosphere View Scheme

(S)-1-(2-(tert-butoxycarbonylamino)acetyl)pyrrolidine-2-carboxylic acid (14296-92-5) → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 0℃; Inert atmosphere;

1-[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)acetyl]-L-proline methyl ester → H-Gly-Pro-OH (704-15-4)

Conditions

Yield

Multi-step reaction with 5 steps 1: lithium hydroxide; water / tetrahydrofuran; methanol / 20 °C 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0 - 20 °C / Inert atmosphere 3: pyridine / 1,4-dioxane / 2 h / 20 °C / Inert atmosphere 4: hydrazine hydrate / ethanol / 3 h / 20 °C / Inert atmosphere 5: water; stenotrophomonas dipeptidyl aminopeptidase IV / aq. buffer / 0.08 h / 37 °C / pH 8 / Enzymatic reaction View Scheme

(S)-1-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-acetyl]-pyrrolidine-2-carboxylic acid → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0 - 20 °C / Inert atmosphere 2: pyridine / 1,4-dioxane / 2 h / 20 °C / Inert atmosphere 3: hydrazine hydrate / ethanol / 3 h / 20 °C / Inert atmosphere 4: water; stenotrophomonas dipeptidyl aminopeptidase IV / aq. buffer / 0.08 h / 37 °C / pH 8 / Enzymatic reaction View Scheme

C15H13ClN2O4 → H-Gly-Pro-OH (704-15-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / 1,4-dioxane / 2 h / 20 °C / Inert atmosphere 2: hydrazine hydrate / ethanol / 3 h / 20 °C / Inert atmosphere 3: water; stenotrophomonas dipeptidyl aminopeptidase IV / aq. buffer / 0.08 h / 37 °C / pH 8 / Enzymatic reaction View Scheme

N-(S)-1-(2-aminoacetyl)-N-(2,4-bis((E)-3,3,3-trifluoroprop-1-en-1-yl)phenyl)pyrrolidine-2-carboxamide → 2,4-bis[(E)-3,3,3-trifluoroprop-1-enyl]aniline + H-Gly-Pro-OH (704-15-4)

Conditions	Yield
With stenotrophomonas dipeptidyl aminopeptidase IV; water In aq. buffer at 37℃; for 0.0833333h; pH=8; Enzymatic reaction;

tert-butyldicarbonate (34619-03-9) + H-Gly-Pro-OH (704-15-4) → (S)-1-(2-(tert-butoxycarbonylamino)acetyl)pyrrolidine-2-carboxylic acid (14296-92-5)

Conditions	Yield
With triethylamine In ethanol at 20 - 60℃; for 4h;	100%

(fluorenylmethoxy)carbonyl chloride (28920-43-6) + H-Gly-Pro-OH (704-15-4) → N-(9H-fluoren-9-ylmethoxycarbonyl)glycyl-L-proline (212651-48-4)

Conditions	Yield
With sodium carbonate In 1,4-dioxane for 3h;	96%

diethyl ether (60-29-7) + zinc(II) hydroxide + H-Gly-Pro-OH (704-15-4) → Zn(2+)*2NH2CH2C(O)NC3H6CHCO2(1-)*H2O*0.1(C2H5)2O=[Zn(NH2CH2C(O)NC3H6CHCO2)2]*H2O*0.1(C2H5)2O

Conditions	Yield
In water Zn(OH)2 was added to aq. soln. of dipeptide; stirred at 60°C for 6 h; stirred at room temp. overnight; filtered; solvent removed; dissolved in methanol/ether (1/1); solvent removed; elem. anal.;	96%

C45H31N9O4Zn + H-Gly-Pro-OH (704-15-4) → C52H41N11O6Zn

Conditions	Yield
Stage #1: C45H31N9O4Zn With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at -5 - 35℃; Inert atmosphere; Stage #2: H-Gly-Pro-OH With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	82.6%

N-benzyloxycarbonyl-L-proline p-nitrophenyl ester (3304-59-4) + H-Gly-Pro-OH (704-15-4) → Z-Pro-Gly-Pro-OH (70989-57-0)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water for 24h;	81%

zinc(II) nitrate hexahydrate + H-Gly-Pro-OH (704-15-4) → [Zn(Gly-Pro)2]

Conditions	Yield
In methanol for 1h;	69%

di-tert-butyl dicarbonate (24424-99-5) + H-Gly-Pro-OH (704-15-4) → (S)-1-(2-(tert-butoxycarbonylamino)acetyl)pyrrolidine-2-carboxylic acid (14296-92-5)

Conditions	Yield
With sodium carbonate In 1,4-dioxane; water	67%

N-(N-benzyloxycarbonyl-glycyl)-thioglycine S-phenyl ester (17126-94-2) + H-Gly-Pro-OH (704-15-4) → H-Gly-Gly-Gly-L-Pro-OH (91307-69-6)

Conditions	Yield
With tetrahydrofuran; methanol; sodium hydroxide Hydrieren des Reaktionsprodukts in Essigsaeure enthaltendem Methanol;

carbon dioxide (124-38-9) + H-Gly-Pro-OH (704-15-4) → (S)-1-(2-Carboxyamino-acetyl)-pyrrolidine-2-carboxylic acid

Conditions	Yield
With borax; sodium dihydrogenphosphate at 26℃; Equilibrium constant;

N-Cbz-L-Phe (1161-13-3) + H-Gly-Pro-OH (704-15-4) → (S)-1-[2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-acetyl]-pyrrolidine-2-carboxylic acid

Conditions	Yield
With pyridine; sodium hydroxide; 5-Nitrobenz<1,6-d>-3H-1,2-oxathiole S,S-dioxide; triethylamine 1) MeCN, 2) MeCN, H2O; Yield given. Multistep reaction;

(2R,3R)-Oxirane-2,3-dicarboxylic acid 2-ethyl ester 3-pentafluorophenyl ester (1027190-58-4) + H-Gly-Pro-OH (704-15-4) → N-<<(2R,3R)-3-trans(ethoxycarbonyl)oxiran-2-yl>carbonyl>-glicyl-proline (159517-32-5)

Conditions	Yield
In N,N-dimethyl-formamide for 24h; Ambient temperature; Yield given;

H-Gly-Pro-OH (704-15-4) → C7H11N2O3 (72634-87-8)

Conditions	Yield
With dipotassium peroxodisulfate; potassium chloride In water Rate constant; Irradiation; Flash-photolysis, pH = 7;;

H-Gly-Pro-OH (704-15-4) → glycine (56-40-6) + L-proline (147-85-3)

Conditions	Yield
With prolidase; (trans)-1,2-cyclopentanedicarboxylic acid; water at 20℃; K+-MES buffer (pH 6.0); Ki value; other inhibitor;

hydrogenchloride (7647-01-0) + H-Gly-Pro-OH (704-15-4) → glycine (56-40-6) + L-proline (147-85-3)

Conditions	Yield
at 100℃; Rate constant; Hydrolysis;

Upstream product

• 60-18-4 L-tyrosine 
• 60189-43-7 H-Gly-Pro-pNA 
• 14296-92-5 (S)-1-(2-(tert-butoxycarbonylamino)acetyl)pyrrolidine-2-carboxylic acid 
• 41863-49-4 t-butyloxycarbonyl-glycyl-proline methyl ester 
• 67341-40-6 7-glycyl-L-prolylamino-4-methylcoumarin 
• 212651-48-4 N-(9H-fluoren-9-ylmethoxycarbonyl)glycyl-L-proline 
• 56-40-6 glycine 
• 147-85-3 L-proline 
• 33256-35-8 H-Pro-Gly-OMe 
• 42761-76-2 glycyl-prolyl-4-methoxy-β-naphthylamide 
• 3705-27-9 (S)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione 
• 2646-61-9 Z-Gly-Pro-Leu-Gly-Pro 
• 72122-62-4 L-tyrosyl-L-prolyl-L-phenylalanyl-L-prolyl-glycyl-L-prolyl-L-isoleucine 
• 837-83-2 gly-pro-ala 

Downstream Products

• 56-40-6 glycine 
• 147-85-3 L-proline 
• 3705-27-9 (S)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione 
• 1262151-59-6 C₂₈H₃₃N₅O₅ 
• 1262151-58-5 C₄₃H₄₃N₅O₇ 
• 67341-40-6 7-glycyl-L-prolylamino-4-methylcoumarin 
• 14296-92-5 (S)-1-(2-(tert-butoxycarbonylamino)acetyl)pyrrolidine-2-carboxylic acid 
• 212651-48-4 N-(9H-fluoren-9-ylmethoxycarbonyl)glycyl-L-proline 
• 82865-27-8 N-Bz-Δ^Z-Phe-Gly-Pro-OH 
• 70989-57-0 Z-Pro-Gly-Pro-OH 
• 82865-32-5 N-(trans-2,4-diphenyl-2-thiazolin-5-ylcarbonyl)glycylproline 

Relevant articles and documents

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

A series of aniline and m-phenylenediamine derivatives with electron-withdrawing 3,3,3-trifluoropropenyl substituents were synthesized as small and chemically stable fluorescent organic compounds. Their fluorescence performances were evaluated by converting 2,4-disubstituted aniline 1 to the non-fluorescent dipeptide analogue H-Gly-Pro-1 for the use as a fluorogenic substrate for dipeptidyl peptidase-4 (DPP-4). The progress of the enzymatic hydrolysis of H-Gly-Pro-1 with DPP-4 was monitored by fluorometric determination of 1 released into the reaction medium. The results suggest that 1 could be used as fluorophore in OFF-ON-type fluorogenic probes.

Zinc(II) complexes of Pro-Gly and Pro-Leu dipeptides: Synthesis, characterization, in vitro DNA binding and cleavage studies

Dipeptide (Pro-Gly and Pro-Leu) Zinc(II) complexes 1 and 2 were designed and synthesized for potential use as cancer chemotherapeutic agents. In order to augment the DNA recognition of metallonuclease activity, zinc metal ion was tethered to peptide motif to carry out DNA site specific hydrolytic cleavage. The structural formulation of the complexes 1 and 2 was done by elemental analysis, spectroscopic methods (IR, NMR, electronic) and molar conductance measurements. Their in vitro DNA binding profile was investigated by UV-vis titrations, fluorescence titrations and circular dichroism which revealed that these complexes bind to CT DNA by electrostatic interactions via groove binding mode. Zn(II) Pro-Gly complex 1 showed greater binding affinity to CT DNA as compared to the Zn(II) Pro-Leu complex 2 due to steric constraints in the latter. The supercoiled pBR322 DNA cleavage activity of complex 1, ascertained by gel electrophoresis demonstrated efficient DNA cleaving ability via hydrolytic mechanistic pathway. Further, the molecular docking studies confirmed that complex 1 bind to the minor groove of DNA having AT-rich sequences with relative binding energy of -196.72 kJ mol-1.

Identification of novel L-amino acid α-ligases through hidden markov model-based profile analysis

L-Amino acid α-ligase (Lal), catalyzing the formation of α-dipeptides from unprotected l-amino acids in an ATP-dependent manner, is used in cost-effective fermentative production of dipeptides. We searched for novel Lals by in silico screening using Hidden Markov Model-based profile analysis, and identified five novel Lals that showed low similarity and different substrate specificity from known Lals.