The Synthesis and Pharmacological Study of 4-Decarboxamido-oxytocin (4-α-Aminobutyric Acid-oxytocin) and 5-Decarboxamido-oxytocin (5-Alanine-oxytocin)

Duvigneaud,; Gs, Denning; Drabarek, Stefania; Chan, WY

doi:10.1016/s0021-9258(18)51704-x

Cited by 37 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Introductionmentioning

confidence: 99%

“…As for the determination of the modification site on peptides, a sophisticated methodology has been developed: peptide scanning. − In this methodology, a systematic substitution of each amino acid in the peptide sequence for a certain scanning unit is used to investigate the importance of the corresponding amino acid residue. Alanine scanning is the most frequently used and classical method among peptide scanning, where the contribution of each amino acid side chain for the activity of the parent peptide can be systematically identified (Figure b). − This adroit approach was followed by the development of other amino acid scanning methods. For example, by d -scanning, the importance of the orientation of each amino acid side chain can be investigated by systematic incorporation of the corresponding d -amino acid for each amino acid residue. − N -Alkyl amino acid scanning can be helpful to investigate the importance of each amide proton as a hydrogen bond donor .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry

et al. 2023

View full text Add to dashboard Cite

Peptides can be converted to highly active compounds by introducing appropriate substituents on the suitable amino acid residue. Although modifiable residues in peptides can be systematically identified by peptide scanning methodologies, there is no practical method for optimization at the "scanned" position. With the purpose of using derivatives not only for scanning but also as a starting point for further chemical functionalization, we herein report the "scanning and direct derivatization" strategy through chemoselective acylation of embedded threonine residues by a serine/threonine ligation (STL) with the help of in situ screening chemistry. We have applied this strategy to the optimization of the polymyxin antibiotics, which were selected as a model system to highlight the power of the rapid derivatization of active scanning derivatives. Using this approach, we explored the structure−activity relationships of the polymyxins and successfully prepared derivatives with activity against polymyxin-resistant bacteria and those with Pseudomonas aeruginosa selective antibacterial activity. This strategy opens up efficient structural exploration and further optimization of peptide sequences.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry

et al. 2023

View full text Add to dashboard Cite

show abstract

“…19 As for the determination of the modification site on peptides, a sophisticated methodology has been developed: peptide scanning. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] In this methodology, the systematic substitution of each amino acid in the peptide sequence for a certain scanning unit is used to investigate the importance of the corresponding amino acid residue.…”

Section: Introductionmentioning

confidence: 99%

“…1b). [20][21][22][23][24][25][26][27][28][29][30][31][32][33] This adroit approach was followed by the development of other amino acid scanning: For example, by D-scanning, the importance of the orientation of each amino acid side chain can be investigated by systematic incorporation of the corresponding D-amino acid for each amino acid residue. [33][34][35] N-Alkyl amino acid scanning can be helpful to investigate the importance of each amide proton as a hydrogen bond donor.…”

Section: Introductionmentioning

confidence: 99%

‘Exploration and Expansion’ in Peptide Sequence: Discovery of Structurally-Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and in situ Screening Chemistry

Kaguchi

Katsuyama

Sato

et al. 2022

Preprint

View full text Add to dashboard Cite

Peptides can be converted to highly active compounds by introducing appropriate substituents on the suitable amino acid residue. Although modifiable residues in peptides can be systematically identified by peptide scanning methodologies, there is no practical method for optimization at the “scanned” position. With the purpose of using derivatives not only for scanning, but also as a starting point for further chemical functionalization, we herein report the ‘exploration and expansion’ strategy through chemoselective acylation of embedded threonine residues by a serine/threonine ligation (STL) with the help of in situ screening chemistry. We have applied this strategy to the optimization of the polymyxin antibiotics, which were selected as a model system to highlight the power of the rapid expansion of active scanning derivatives. Using this approach, we explored the structure-activity relationships of the polymyxins and successfully prepared derivatives with activity against polymyxin-resistant bacteria and those with P. aeruginosa selective antibacterial activity. This strategy opens up efficient structural exploration and further optimization of peptide sequences.

show abstract

Design of Cyclic Peptides

Demmer

Frank

Kessler

2009

Peptide and Protein Design for Biopharmaceutical Applications

View full text Add to dashboard Cite

The Synthesis and Pharmacological Study of 4-Decarboxamido-oxytocin (4-α-Aminobutyric Acid-oxytocin) and 5-Decarboxamido-oxytocin (5-Alanine-oxytocin)

Cited by 37 publications

References 32 publications

Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry

Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry

‘Exploration and Expansion’ in Peptide Sequence: Discovery of Structurally-Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and in situ Screening Chemistry

Design of Cyclic Peptides

Contact Info

Product

Resources

About