Use of the 2‐chlorotrityl chloride resin for microwave‐assisted solid phase peptide synthesis

Ieronymaki, Matthaia; Androutsou, Maria Eleni; Pantelia, Anna; Friligou, Irene; Crisp, Molly; High, Kirsty Elizabeth; Penkman, Kirsty; Gatos, Dimitrios; Tselios, Theodore

doi:10.1002/bip.22710

Cited by 28 publications

(26 citation statements)

References 40 publications

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“…One gram of CTC resin (16) (1.2 mmol/g) was placed in a polypropylene reaction vessel fitted with a polypropylene frit. The resin was swollen with dry DCM (10 mL/gram of resin) for 30 minutes after which the solvent was removed.…”

Section: Methodsmentioning

confidence: 99%

Peptide ligands for targeting the extracellular domain of EGFR: Comparison between linear and cyclic peptides

et al. 2017

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Colorectal cancer (CRC) is the third most common solid internal malignancy among cancers. Early detection of cancer is key to increasing the survival rate of colorectal cancer patients. Overexpression of the EGFR protein is associated with CRC. We have designed a series of peptides that are highly specific for the extracellular domain of EGFR, based on our earlier studies on linear peptides. The previously reported linear peptide LARLLT, known to bind to EGFR, was modified with the goals of increasing its stability and its specificity toward EGFR. Peptide modifications, including D-amino acid substitution, cyclization, and chain reversal, were investigated. In addition, to facilitate labeling of the peptide with a fluorescent dye, an additional lysine residue was introduced onto the linear (KLARLLT) and cyclic peptides cyclo(KLARLLT) (Cyclo.L1). The lysine residue was also converted into an azide group in both a linear and reversed cyclic peptide sequences cyclo(K(N3)larllt) (Cyclo.L1.1) to allow for subsequent "click" conjugation. The cyclic peptides showed enhanced binding to EGFR by SPR. NMR and molecular modeling studies suggest that the peptides acquire a β-turn structure in solution. In vitro stability studies in human serum show that the cyclic peptide is more stable than the linear peptide.

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Section: Methodsmentioning

confidence: 99%

Peptide ligands for targeting the extracellular domain of EGFR: Comparison between linear and cyclic peptides

et al. 2017

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“…The linear M2TM C-terminally amidated peptide, SSDPLVVAASIIGILHLILWILDRL-CONH 2 , corresponding to residues 22-46 of Udorn/72 wild type sequence of M2 protein was synthesized on 2chlorotrityl chloride resin conjugated with the Rink Amide linker, using the Fmoc/tBu solid-phase methodology and a standard synthetic protocol. [33][34][35][36][37] The first N α Fmoc -protected rink amide linker [4-[(2,4-Dimethoxyphenyl)(Fmoc-amino)methyl]phenoxyacetic acid] was esterified to the resin in the presence of N,N-diisopropylethylamine (DIEA) in dichloromethane. The protected peptide was synthesized on the resin by sequential couplings of the appropriate Fmoc protected amino acids, in the presence of N,N′diisopropylcarbodiimide (DIC) and 1-hydroxybenzotriazole (HOBT) in N,N-dimethylformamide (DMF).…”

Section: M2tm Peptide Synthesismentioning

confidence: 99%

Influenza A M2 Spans the Membrane Bilayer, Perturbs its Organization and Differentiates the Effect of Amantadine and Spiro[pyrrolidine-2,2'-adamantane] AK13 on Lipids

Konstantinidi¹,

Naziris²,

Sartori³

et al. 2019

Preprint

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The investigation and observations made for the M2TM, excess aminoadamantane ligands in DMPC were made using the simpler version of biophysical methods including SDC, SAXS and WAXS, MD simulations and ssNMR. 1H, 31P ssNMR and MD simulations, showed that M2TM in apo form or drug-bound form span the membrane interacting strongly with lipid acyl chain tails and the phosphate groups of the polar head surface. The MD simulations showed that the drugs anchor through their ammonium group with the lipid phosphate and occasionally with M2TM asparagine-44 carboxylate groups. The 13C ssNMR experiments allow the inspection of excess drug molecules and the assessment of its impact on the lipid head-group region. At low peptide concentrations of influenza A M2TM tetramer in DPMC bilayer, two lipid domains were observed that likely correspond to the M2TM boundary lipids and the bulk-like lipids. At high peptide concentrations, one domain was identified which constitute essentially all of the lipids which behave as boundary. This effect is likely due, according to the MD simulations, to the preference of AK13 to locate in closer vicinity to M2TM compared to Amt as well as the stronger ionic interactions of Amt primary ammonium group with phosphate groups, compared with the secondary buried ammonium group in AK13.<br>

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“…The linear-Cit protected peptide (H-Val-His(Trt)-Phe-Phe-Cit 91 -Asn(Trt)-Ile-Val-Thr(tBu)-Ala 96 -Cit 97 -Thr(tBu)-Pro-OH was synthesized on 2-chlorotrityl chloride resin (CTLR-Cl) using the Fmoc/tBu methodology (Scheme 3). 25,[50][51][52] The Fmoc-protected amino acids were purchased from CBL (Chemical and Biopharmaceutical Laboratories, Patras, Greece). The peptide was synthesized manually on a 0.5 mmol scale, following convergent protocol of solid phase peptide synthesis, up to the final protected analog.…”

Section: Solid-phase Peptide Synthesis Of Cyclic-citmentioning

confidence: 99%

Cyclic citrullinated MBP87–99 peptide stimulates T cell responses: Implications in triggering disease

Apostolopoulos

Deraos

Matsoukas

et al. 2017

Bioorganic & Medicinal Chemistry

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Amino acid mutations to agonist peptide epitopes of myelin proteins have been used to modulate immune responses and experimental autoimmune encephalomyelitis (EAE, animal model of multiple sclerosis). Such amino acid alteration are termed, altered peptide ligands (APL). We have shown that the agonist myelin basic protein (MBP) 87-99 epitope (MBP) with crucial T cell receptor (TCR) substitutions at positions 91 and 96 (K,P (TCR contact residues) to R,A; [R,A]MBP) results in altered T cell responses and inhibits EAE symptoms. In this study, the role of citrullination of arginines in [R,A]MBP peptide analog was determined using in vivo experiments in combination with computational studies. The immunogenicity of linear [Cit,A,Cit]MBP and its cyclic analog - cyclo(87-99)[Cit,A,Cit]MBP when conjugated to the carrier mannan (polysaccharide) were studied in SJL/J mice. It was found that mannosylated cyclo(87-99)[Cit,A,Cit]MBP peptide induced strong T cell proliferative responses and IFN-gamma cytokine secretion compared with the linear one. Moreover, the interaction of linear and cyclic peptide analogs with the major histocompatibility complex (MHC II, H2-IA) and TCR was analyzed using molecular dynamics simulations at the receptor level, in order to gain a better understanding of the molecular recognition mechanisms that underly the different immunological profiles of citrullinated peptides compared to its agonist native counterpart MBP epitope. The results demonstrate that the citrullination of arginine in combination with the backbone conformation of mutated linear and cyclic analogs are significant elements for the immune response triggering the induction of pro-inflammatory cytokines.

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Use of the 2‐chlorotrityl chloride resin for microwave‐assisted solid phase peptide synthesis

Cited by 28 publications

References 40 publications

Peptide ligands for targeting the extracellular domain of EGFR: Comparison between linear and cyclic peptides

Peptide ligands for targeting the extracellular domain of EGFR: Comparison between linear and cyclic peptides

Influenza A M2 Spans the Membrane Bilayer, Perturbs its Organization and Differentiates the Effect of Amantadine and Spiro[pyrrolidine-2,2'-adamantane] AK13 on Lipids

Cyclic citrullinated MBP87–99 peptide stimulates T cell responses: Implications in triggering disease

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