2799-07-7

Basic information

• Product Name: S-Trityl-L-cysteine
• Synonyms: 3-(tritylthio)-l-alanin;3-tritylthio-l-alanine;s-(triphenylmethyl)-l-cystein;H-CYS(TRT)-OH;CYSTEINE(TRT)-OH;EG5 INHIBITOR II;NSC 83265;S-(TRIPHENYLMETHYL)-L-CYSTEINE
• CAS NO: 2799-07-7
• Molecular Formula: C₂₂H₂₁NO₂S
• Molecular Weight: 363.47
• EINECS: 218-195-8
• Product Categories: Amino Acids Derivatives;Cysteine [Cys, C];Amino Acids and Derivatives;Amino Acids 13C, 2H, 15N;Amino Acid Derivatives;Amino Acids & Derivatives;Aromatics;Chiral Reagents;Enzyme substrates;Cell Cycle Regulation
• Mol File: 2799-07-7.mol

Chemical Properties

• Melting Point: 182-183 °C (dec.)(lit.)
• Boiling Point: 524.7 °C at 760 mmHg
• Flash Point: 271.2 °C
• Appearance: almost white to light yellow granular powder
• Density: 1.1342 (rough estimate)
• Vapor Pressure: 7.71E-12mmHg at 25°C
• Refractive Index: 111 ° (C=0.8, 0.04mol Ethanolic HCl)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 20 mg/ml).
• PKA: 2.22±0.10(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 week.
• BRN: 2339626
• CAS DataBase Reference: S-Trityl-L-cysteine(CAS DataBase Reference)
• NIST Chemistry Reference: S-Trityl-L-cysteine(2799-07-7)
• EPA Substance Registry System: S-Trityl-L-cysteine(2799-07-7)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 22-24/25
• WGK Germany: 3
• RTECS: AY7710000
• Hazardous Substances Data: 2799-07-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
S-Trityl-L-cysteine is used as a protected cysteine for peptide synthesis, which is essential in the development of various pharmaceutical compounds. Its role in inhibiting the mitotic kinesin Eg5 makes it a potential candidate for the development of anti-cancer drugs, as it can prevent mitotic progression and exhibit antitumor activity.
Used in Chemical Synthesis:
S-Trityl-L-cysteine is used as a reagent in solution phase peptide synthesis (SPPS), where it aids in the formation of peptide bonds and contributes to the synthesis of complex peptide structures.
Used in Cation-Sensing Applications:
S-Trityl-L-cysteine is used as a metal-binding agent to synthesize substituted ferrocenoyl peptide conjugates using HBTU peptide coupling reagent. This application is particularly relevant in the development of cation-sensing solutions, where peptide-metal interactions are crucial for detecting and analyzing the presence of specific metal ions.

Biological Activity

Potent, cell-permeable, selective inhibitor of mitotic kinesin Eg5, a protein required for establishing and maintaining a bipolar spindle. Inhibits basal ATPase activity (IC 50 = 1 mM) and microtubule-activated ATPase activity of Eg5 (IC 50 = 140 nM). Induces mitotic arrest in HeLa cells with an IC 50 of 700 nM. Displays antitumor activity.

References

1) DeBonis et al. (2004) In vitro screening for inhibitors of the human mitotic kinesin Eg5 with antimitotic and antitumour activities; Mol. Cancer Ther. 3 1079 2) Brier et al. (2004) Identification of the protein binding region of S-trityl-L-cysteine, a new potent inhibitor of mitotic kinesin Eg5; Biochemistry 43 13072 3) Skoufias et al. (2006) S-trityl-l-cysteine is a reversible, tight-binding inhibitor of the human kinesin eg5 that specifically blocks mitotic progression; J. Biol. Chem., 281 17559

InChI:InChI=1/C22H21NO2S/c23-20(21(24)25)16-26-22(17-10-4-1-5-11-17,18-12-6-2-7-13-18)19-14-8-3-9-15-19/h1-15,20H,16,23H2,(H,24,25)

Upstream product

• 76-83-5 trityl chloride 
• 93-58-3 benzoic acid methyl ester 
• 100-59-4 phenylmagnesium chloride 
• 591-51-5 phenyllithium 
• 52-89-1 l-cysteine hydrochloride 
• 32443-99-5 D-cysteine hydrochloride 
• 76-84-6 triphenylmethyl alcohol 
• 921-01-7 D-cysteine 
• 103213-32-7 N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine 
• 52-90-4 L-Cysteine 
• 880762-43-6 trifluoromethanesulfonic acid (R)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl ester 

Downstream Products

• 21947-98-8 N-tert-butyloxycarbonyl-S-trityl-L-cysteine 
• 27686-50-6 N,S-Ditrityl-L-Cystein 
• 26988-59-0 N-Boc-S-trityl-L-cysteine dicyclohexylamine salt 
• 62675-68-7 S-(triphenylmethyl)-L-cysteine methyl ester hydrochloride 
• 1159989-15-7 C₄₀H₃₆N₂O₆S 
• 1269512-11-9 C₅₈H₅₀N₂O₈S₂ 
• 1269512-13-1 C₅₈H₅₀N₂O₈S₂ 
• 1269512-15-3 C₅₈H₅₀N₂O₈S₂ 
• 1446417-07-7 (2R,2'R)-2,2'-(([2,2'-biquinoline]-4,4'-dicarbonyl)bis(azanediyl))bis(3-(tritylthio)propanoic acid) 
• 1446417-09-9 (R)-2-((E)-4-(((R)-1-carboxy-2-(tritylthio)ethyl)amino)-4-oxobut-2-enamido)-3-(tritylthio)propanoic acid 
• 1446417-12-4 (R)-2-((Z)-4-(((R)-1-carboxy-2-(tritylthio)ethyl)amino)-4-oxobut-2-enamido)-3-(tritylthio)propanoic acid 
• 1446417-14-6 (R)-2-(6-(((R)-1-carboxy-2-(tritylthio)ethyl)amino)-6-oxohexanamido)-3-(tritylthio)propanoic acid 
• 1446417-16-8 (R)-2-(8-(((R)-1-carboxy-2-(tritylthio)ethyl)amino)-8-oxooctanamido)-3-(tritylthio)propanoic acid 
• 1446416-89-2 (2R,2'R)-2,2'-((thiophene-2,3-dicarbonyl)bis(azanediyl))bis(3-(tritylthio)propanoic acid) 

Relevant articles and documents

Palladium Mediated Rapid Deprotection of N-Terminal Cysteine under Native Chemical Ligation Conditions for the Efficient Preparation of Synthetically Challenging Proteins

Facilitating the process of chemical protein synthesis is an important goal in order to enable the efficient preparation of large and novel protein analogues. Native chemical ligation, which is widely used in the synthesis and semisynthesis of proteins, has been going through several developments to expedite the synthetic process and to obtain the target protein in high yield. A key aspect of this approach is the utilization of protecting groups for the N-terminal Cys in the middle fragments, which bear simultaneously the two reactive groups, i.e., N-terminal Cys and C-terminal thioester. Despite important progress in this area, as has been demonstrated in the use of thiazolidine protecting group in the synthesis of over 100 proteins, finding optimal protecting group(s) remains a challenge. For example, the thiazolidine removal step is very slow (>8 h), and in some cases the applied conditions lead to undesired side reactions. Here we show that water-soluble palladium(II) complexes are excellent reagents for the effective unmasking of thiazolidine, enabling its complete removal within 15 min under native chemical ligation conditions. Moreover, palladium is also able to rapidly remove propargyloxycarbonyl-protecting group from the N-terminal Cys in a similar efficiency. The utility of the new removal conditions for both protecting groups is exemplified in the rapid and efficient synthesis of Lys34-ubiquitinated H2B and for the first time neddlyated peptides derived from cullin1. The current approach expands the use of palladium in protein chemistry and should significantly facilitate the chemical and semisynthesis of synthetically challenging proteins from multiple fragments.

3-Mercaptopropionic acid-mediated synthesis of peptide and protein thioesters

Peptides and proteins fragment sequence-specifically in the presence of 3-mercaptopropionic acid to afford thioesters which can be used in native chemical ligation reactions. The Royal Society of Chemistry.

Expeditious and practical synthesis of tertiary alcohols from esters enabled by highly polarized organometallic compounds under aerobic conditions in Deep Eutectic Solvents or bulk water

An efficient protocol was developed for the synthesis of tertiary alcohols via nucleophilic addition of organometallic compounds of s-block elements (Grignard and organolithium reagents) to esters performed in the biodegradable choline chloride/urea eutectic mixture or in water. This approach displays a broad substrate scope, with the addition reaction proceeding quickly (20 s reaction time) and cleanly, at ambient temperature and under air, straightforwardly furnishing the expected tertiary alcohols in yields of up to 98%. The practicability of the method is exemplified by the sustainable synthesis of some representative S-trityl-L-cysteine derivatives, which are a potent class of Eg5 inhibitors, also via telescoped one-pot processes.

Polycysteine as a new type of radio-protector ameliorated tissue injury through inhibiting ferroptosis in mice

Amifostine has been the only small molecule radio-protector approved by FDA for decades; however, the serious adverse effects limit its clinical use. To address the toxicity issues and maintain the good potency, a series of modified small polycysteine peptides had been prepared. Among them, compound 5 exhibited the highest radio-protective efficacy, the same as amifostine, but much better safety profile. To confirm the correlation between the radiation-protective efficacy and the DNA binding capability, each of the enantiomers of the polycysteine peptides had been prepared. As a result, the l-configuration compounds had obviously higher efficacy than the corresponding d-configuration enantiomers; among them, compound 5 showed the highest DNA binding capability and radiation-protective efficacy. To our knowledge, this is the first study that has proved their correlations using direct comparison. Further exploration of the mechanism revealed that the ionizing radiation (IR) triggered ferroptosis inhibition by compound 5 could be one of the pathways for the protection effect, which was different from amifostine. In summary, the preliminary result showed that compound 5, a polycysteine as a new type of radio-protector, had been developed with good efficacy and safety profile. Further study of the compound for potential use is ongoing.

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and in Vivo Biological Evaluation for Acute Lung Injury

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a nat

Convergent Total Synthesis of the Siderophore Piscibactin as Its Ga3+Complex

The siderophore piscibactin is a key virulence factor involved in the iron uptake of pathogenic bacteria Photobacterium damselae subsp. piscicida and Vibrio anguillarum, responsible for the fish diseases photobacterioisis (pasteurellosis) and vibriosis, respectively. A convergent total synthesis of its Ga3+ complex using l-/d-cysteine as chiral agents and Meldrum's acid is described. A Staudinger reduction/Aza-Wittig process in the synthesis of the acid-sensitive β-hydroxy-2,4-disubstituted thiazoline moiety and the convenient protecting groups was a key step in this synthesis.

Design, Synthesis, and Conformation-Activity Study of Unnatural Bridged Bicyclic Depsipeptides as Highly Potent Hypoxia Inducible Factor-1 Inhibitors and Antitumor Agents

By carrying out structural modifications based on the bicyclic peptide structure of echinomycin, we successfully synthesized various powerful antitumor derivatives. The ring conformation in the obtained compounds was restricted by cross-linking with an unnatural bond. The prepared derivatives were demonstrated to strongly suppress the hypoxia inducible factor (HIF)-1 transcriptional activation and hypoxia induction of HIF-1 protein expression. Particularly, alkene-bridged derivative 12 exhibited remarkably potent cytotoxicity (IC50 = 0.22 nM on the MCF-7 cell line) and HIF-1 inhibition (IC50 = 0.09 nM), which considerably exceeded those of echinomycin. Conformational analyses and molecular modeling studies revealed that the biological activities were enhanced following restriction of the conformation by cross-linking through a metabolically stable and rigid bridge bond. In addition, we proposed a new globular conformation stabilized by intramolecular πstacking that can contribute to the biological effects of bicyclic depsipeptides. The developments presented in the current study serve as a useful guide to expand the chemical space of peptides in drug discovery.

Tripeptide-induced modulation of mesenchymal stem cell biomechanics stimulates proliferation and wound healing

We demonstrate the ability of two tripeptides to promote proliferation and modulate the mechanical properties of human mesenchymal stem cells (hMSCs). Notably, Young's modulus of peptide-treated hMSCs was found to be ～2 fold higher compared to the control group. These peptides promoted wound healing in hMSCs, without stimulating osteogenic and adipogenic differentiation, thus showing high potential in vascular tissue engineering applications.

Aminothiol compound, preparation method of aminothiol compound and application of aminothiol compound in radiation protection

The invention discloses an aminothiol compound, a preparation method of the aminothiol compound and application of the aminothiol compound in radiation protection. The compound has a structure shown in the formula I in the description, wherein A1 is selected from -C(O)NR8-, -S(O)2-NR8-, -S(O)NR8- and -R7-NR8-, A2 is selected from carbonyl, sulfonyl, sulfinyl and substituted or unsubstituted C1-6 alkyl, R1, R2, R5 and R6 can be the same or not and are selected from hydrogen and substituted or unsubstituted C1-C5 alkyl or hetero alkyl, n is an integer from 0 to 20000, R3 and R4 are independently selected from hydrogen, X and substituted or unsubstituted C1-6 alkyl, X is selected from F, Cl, Br and I, R7 is selected from substituted or unsubstituted C1-C6 alkyl, and R8 is selected from hydrogen and substituted or unsubstituted C1-C6 alkyl. The compound has the effect of reducing biological injury caused by ionizing radiation and also has the effects of prolonging the lifetime of radiated animals and increasing the survival rate of the radiated animals.

A "catch-and-release" protocol for alkyne-tagged molecules based on a resin-bound cobalt complex for peptide enrichment in aqueous media

The development of new and mild protocols for the specific enrichment of biomolecules is of significant interest from the perspective of chemical biology. A cobalt-phosphine complex immobilised on a solid-phase resin has been found to selectively bind to a propargyl carbamate tag, that is, "catch", under dilute aqueous conditions (pH 7) at 4-°C. Upon acidic treatment of the resulting resin-bound alkyne-cobalt complex, the Nicholas reaction was induced to "release" the alkyne-tagged molecule from the resin as a free amine. Model studies revealed that selective enrichment of the alkyne-tagged molecule could be achieved with high efficiency at 4-°C. The proof-of-concept was applied to an alkyne-tagged amino acid and dipeptide. Studies using an alkyne-tagged dipeptide proved that this protocol is compatible with various amino acids bearing a range of functionalities in the side-chain. In addition, selective enrichment and detection of an amine derived from the "catch and release" of an alkyne-tagged dipeptide in the presence of various peptides has been accomplished under highly dilute conditions, as determined by mass spectrometry. Catch and release: The specific enrichment of alkyne-tagged molecules has been achieved by using cobalt beads. A cobalt complex bound to a resin was found to selectively "catch" a propargyl carbamate tag under dilute aqueous conditions (see scheme). Upon acidic treatment of the alkyne-cobalt complex, the Nicholas reaction was induced to "release" an amine. Studies using an alkyne-tagged dipeptide proved its compatibility with various amino acids and peptides under highly dilute conditions.