Re-evaluation of the N-terminal substitution and the D-residues of teixobactin

Monaim, Shimaa A. H. Abdel; Jad, Yahya E.; Acosta, Gerardo; Naicker, Tricia; Ramchuran, Estelle J.; El‐Faham, Ayman; Govender, Thavendran; Kruger, Hendrik G.; Torre, Beatriz G. de la; Alberício, Fernando

doi:10.1039/c6ra17720d

Cited by 35 publications

(30 citation statements)

References 12 publications

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“…Because d -Thr is essential for creating the ester bond and to build up the depsipeptide cycle, the corresponding lysine analogue at the bridgehead position 8 was not prepared. Also, neither the analogue at position 1 (importance was previously established by our group) 10 nor the one at position 10 (reported by the group of Nowick and co-workers) 15 was investigated in this study. The eight lysine analogues covered the substitution of the four hydrophobic isoleucine (represented by the red color in Figure 2), the three polar uncharged residues 2× serine, glutamine(represented by the green color in Figure 2), and the neutral alanine (represented by the yellow color in Figure 2) by lysine.…”

Section: Results and Discussionmentioning

confidence: 98%

“…7,10 Succinctly, the synthesis was started by anchoring a residue at position 9 [Fmoc-Ala-OH or Fmoc-Lys(Boc)-OH in the case of the Lys 9 analogue] to a chlorotrityl chloride polystyrene resin (CTC-resin), and then the elongation of the peptide chain was achieved by the use of Fmoc-amino acids until residue at position 6 (isoleucine or lysine in the case of the Lys 6 analogue, in all cases except in the synthesis where Lys 11 analogue). Then, the β-hydroxyl functional group of d -Thr, which had been incorporated without protection, was acylated by Alloc- l -Ile-OH, followed by the incorporation of Alloc-Arg(Pbf)-OH.…”

Section: Methodsmentioning

confidence: 99%

“…The minimum inhibitory concentration (MIC) was determined as previously described, with meropenem as the control (see the Supporting Information). 10 …”

Section: Methodsmentioning

confidence: 99%

“…This was also observed when the N -Me- d -Phe at the N -terminal was substituted with N -Ac- d -Phe, indicating the importance of a positive charge at the N -terminal. 8,10 …”

Section: Introductionmentioning

confidence: 99%

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Lysine Scanning of Arg₁₀–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues

Monaim¹,

Jad²,

Ramchuran³

et al. 2016

ACS Omega

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Teixobactin is a recently discovered antimicrobial cyclodepsipeptide with good activity against Gram positive bacteria. Taking Arg10–teixobactin as a reference, where the nonproteinogenic residue l-allo-enduracididine was substituted by arginine, a lysine scan was performed to identify the importance of keeping the balance between hydrophilic and hydrophobic amino acids for the antimicrobial activities of this peptide family. Thus, the substitution of four isoleucine residues present in the natural sequence by lysine led to a total loss of activity. On the other hand, the substitution of the polar noncharged residues and alanine by lysine allowed us to keep and in some cases to improve the antimicrobial activity.

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Section: Results and Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

“…The minimum inhibitory concentration (MIC) was determined as previously described, with meropenem as the control (see the Supporting Information). 10 …”

Section: Methodsmentioning

confidence: 99%

“…This was also observed when the N -Me- d -Phe at the N -terminal was substituted with N -Ac- d -Phe, indicating the importance of a positive charge at the N -terminal. 8,10 …”

Section: Introductionmentioning

confidence: 99%

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Lysine Scanning of Arg₁₀–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues

Monaim¹,

Jad²,

Ramchuran³

et al. 2016

ACS Omega

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“…Abdel Monaim et al . reported the total synthesis of many analogues of teixobactin ( 27 ; Figure ) by using two cyclization methods either in solution or on a solid support.…”

Section: Bacterial Antimicrobial Cyclopeptidesmentioning

confidence: 99%

Bacteria Hunt Bacteria through an Intriguing Cyclic Peptide

et al. 2018

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In the last few decades, peptides have been victorious over small molecules as therapeutics due to their broad range of applications, high biological activity, and high specificity. However, the main challenges to overcome if peptides are to become effective drugs is their low oral bioavailability and instability under physiological conditions. Cyclic peptides play a vital role in this context because they show higher stability under physiological conditions, higher membrane permeability, and greater oral bioavailability than that of their corresponding linear analogues. In this regard, cyclic antimicrobial peptides (AMPs) have gained considerable attention in the field of novel antibiotic development. Bacterial strains produce cyclic AMPs through two pathways: ribosomal and nonribosomal. This review provides an overview of the chemical classification of cyclic AMPs isolated from bacteria, and provides a description of their biological activity and mode of action.

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Chemistry and Biology of Teixobactin

Guo

Mandalapu

et al. 2017

Chemistry A European J

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Bacterial resistance to existing drugs is becoming a serious public health issue, urging extensive search for new antibiotics. Teixobactin, a cyclic depsipeptide discovered in a screen of uncultured bacteria, shows potent activity against all the tested Gram-positive bacteria. Remarkably, no teixobactin-resistant bacterial strain has been obtained despite extensive efforts, highlighting the great potential of teixobactin as a lead compound in the fight against antimicrobial resistance (AMR). This review summarizes recent progresses in the understanding of many aspects of teixobactin, including chemical structure, biological activity, biosynthetic pathway, and mode of action. We also discuss the different synthetic strategies in producing teixobactin and its analogues, and the structure-activity relationship (SAR) studies.

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Re-evaluation of the N-terminal substitution and the D-residues of teixobactin

Abstract: Teixobactin is a head to side-chain cyclic depsipeptide with a guanidino based residue within the cycle, three d-amino acids in the tail, and a N-methylated terminal residue.

Cited by 35 publications

References 12 publications

Lysine Scanning of Arg₁₀–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues

Lysine Scanning of Arg₁₀–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues

Bacteria Hunt Bacteria through an Intriguing Cyclic Peptide

Chemistry and Biology of Teixobactin

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Re-evaluation of the N-terminal substitution and the D-residues of teixobactin

Abstract: Teixobactin is a head to side-chain cyclic depsipeptide with a guanidino based residue within the cycle, three d-amino acids in the tail, and a N-methylated terminal residue.

Cited by 35 publications

References 12 publications

Lysine Scanning of Arg10–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues

Lysine Scanning of Arg10–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues

Bacteria Hunt Bacteria through an Intriguing Cyclic Peptide

Chemistry and Biology of Teixobactin

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Product

Resources

About

Lysine Scanning of Arg₁₀–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues

Lysine Scanning of Arg₁₀–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues