UPS on Weinreb Resin:  A Facile Solid-Phase Route to Aldehyde and Ketone Derivatives of “Unnatural” Amino Acids and Peptides

2000 ◽  
Vol 2 (2) ◽  
pp. 172-181 ◽  
Author(s):  
Martin J. O'Donnell ◽  
Mark D. Drew ◽  
Richard S. Pottorf ◽  
William L. Scott
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Solid Phase ◽  
Derivatives Of

The solid phase synthesis of α,α-disubstituted unnatural amino acids and peptides (di-UPS)

1997 ◽  
Vol 38 (21) ◽  
pp. 3695-3698 ◽  
Author(s):  
William L. Scott ◽  
Changyou Zhou ◽  
Zhiqiang Fang ◽  
Martin J. O'Donnell
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Phase Synthesis

A Solid-Phase Synthetic Route to Unnatural Amino Acids with Diverse Side-Chain Substitutions

2002 ◽  
Vol 67 (9) ◽  
pp. 2960-2969 ◽  
Author(s):  
William L. Scott ◽  
Martin J. O'Donnell ◽  
Francisca Delgado ◽  
Jordi Alsina
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Solid Phase ◽  
Side Chain ◽  
Synthetic Route

Solid-phase synthesis of unnatural amino acids using unactivated alkyl halides

1997 ◽  
Vol 38 (41) ◽  
pp. 7163-7166 ◽  
Author(s):  
Martin J. O'Donnell ◽  
Charles W. Lugar ◽  
Richard S. Pottorf ◽  
Changyou Zhou ◽  
William L. Scott ◽  
...  
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Alkyl Halides ◽  
Phase Synthesis

Solid-phase synthesis and utilization of side-chain reactive unnatural amino acids

2003 ◽  
Vol 44 (46) ◽  
pp. 8403-8406 ◽  
Author(s):  
Martin J. O'Donnell ◽  
Jordi Alsina ◽  
William L. Scott
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Side Chain ◽  
Phase Synthesis

scholarly journals Synthesis of Fmoc-Triazine Amino Acids and Its Application in the Synthesis of Short Antibacterial Peptidomimetics

2020 ◽  
Vol 21 (10) ◽  
pp. 3602
Author(s):  
Pethaiah Gunasekaran ◽  
Eun Young Kim ◽  
Jian Lee ◽  
Eun Kyoung Ryu ◽  
Song Yub Shin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Unnatural Amino Acids ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Proteolytic Degradation ◽  
Antibacterial Resistance ◽  
Hydrophobic Residues ◽  
Intracellular Targeting ◽  
Proteolytic Stability

To combat the escalating rise of antibacterial resistance, the development of antimicrobial peptides (AMPs) with a unique mode of action is considered an attractive strategy. However, proteolytic degradation of AMPs remains the greatest challenge in their transformation into therapeutics. Herein, we synthesized Fmoc-triazine amino acids that differ from each other by anchoring either cationic or hydrophobic residues. These unnatural amino acids were adopted for solid-phase peptide synthesis (SPPS) to synthesize a series of amphipathic antimicrobial peptidomimetics. From the antimicrobial screening, we found that the trimer, BJK-4 is the most potent short antimicrobial peptidomimetic without showing hemolytic activity and it displayed enhanced proteolytic stability. Moreover, the mechanism of action to kill bacteria was found to be an intracellular targeting.

scholarly journals Structure-guided protein engineering of ammonia lyase for efficient synthesis of sterically bulky unnatural amino acids

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Zi-Fu Ni ◽  
Pei Xu ◽  
Min-Hua Zong ◽  
Wen-Yong Lou
Keyword(s):  
Amino Acids ◽  
Protein Engineering ◽  
Unnatural Amino Acids ◽  
Solid Phase ◽  
Screening Method ◽  
Fold Increase ◽  
Catalyst System ◽  
Binding Pocket ◽  
Drug Synthesis ◽  
Combined Mutagenesis

AbstractEnzymatic asymmetric amination addition is seen as a promising approach for synthesizing amine derivatives, especially unnatural amino acids, which are valuable precursors to fine chemicals and drugs. Despite the broad substrate spectrum of methylaspartate lyase (MAL), some bulky substrates, such as caffeic acid, cannot be effectively accepted. Herein, we report a group of variants structurally derived from Escherichia coli O157:H7 MAL (EcMAL). A combined mutagenesis strategy was used to simultaneously redesign the key residues of the entrance tunnel and binding pocket to explore the possibility of accepting bulky substrates with potential application to chiral drug synthesis. Libraries of residues capable of lining the active center of EcMAL were then constructed and screened by an effective activity solid-phase color screening method using tyrosinase as a cascade catalyst system. Activity assays and molecular dynamics studies of the resultant variants showed that the substrate specificity of EcMAL was modified by adjusting the polarity of the binding pocket and the degree of flexibility of the entrance tunnel. Compared to M3, the optimal variant M8 was obtained with a 15-fold increase in catalytic activity. This structure-based protein engineering of EcMAL can be used to open new application directions or to develop practical multi-enzymatic processes for the production of various useful compounds.

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