Vectorization via Siderophores Increases Antibacterial Activity of K(RW) Peptides against Pseudomonas aeruginosa.

A series of new conjugates comprised from a small synthetic antimicrobial peptide (AMP) and a siderophore-type vector component was designed and tested for activity on P. aeruginosa PAO1 and several genetically modified strains. As AMP, the well-established arginine-tryptophane combination K(RW) (P1) was chosen with an added lysine for siderophore attachment.

T cells of colorectal cancer patients' stimulated by neoantigenic and cryptic peptides better recognize autologous tumor cells.

Background: Patients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells (Tc).

Methods: Colorectal cancers (CRC) HROC113 and HROC285 were selected based on high TMB, microsatellite instability and HLA class I expression. Their HLA ligandome was characterized using mass spectrometry, compared with the HLA ligand atlas and HLA class I-binding affinity was predicted.

The diversity and utility of arylthiazoline and aryloxazoline siderophores: challenges of total synthesis.

Siderophores are unique ferric ion chelators produced and secreted by some organisms like bacteria, fungi and plants under iron deficiency conditions. These molecules possess immense affinity and specificity for Fe and other metal ions, which attracts great interest due to the numerous possibilities of application, including antibiotics delivery to resistant bacteria strains. Total synthesis of siderophores is a must since the compounds are present in natural sources at extremely small concentrations.

Covalent Docking Identifies a Potent and Selective MKK7 Inhibitor.

The c-Jun NH2-terminal kinase (JNK) signaling pathway is central to the cell response to stress, inflammatory signals, and toxins. While selective inhibitors are known for JNKs and for various upstream MAP3Ks, no selective inhibitor is reported for MKK7--one of two direct MAP2Ks that activate JNK. Here, using covalent virtual screening, we identify selective MKK7 covalent inhibitors.

Ferrichrome Has Found Its Match: Biomimetic Analogues with Diversified Activity Map Discrete Microbial Targets.

Siderophores provide an established platform for studying molecular recognition principles in biological systems. Herein, the preparation of ferrichrome (FC) biomimetic analogues varying in length and polarity of the amino acid chain separating between the tripodal scaffold and the pendent Fe chelating hydroxamic acid groups was reported. Spectroscopic and potentiometric titrations determined their iron affinity to be within the range of efficient chelators.

Biomimetic ferrichrome: structural motifs for switching between narrow- and broad-spectrum activities in P. putida and E. coli.

A series of novel ferrichrome (FC) analogs was designed based on the X-ray structure of FC in the FhuA transporter of Escherichia coli. Two strategies were employed: the first strategy optimized the overall size and relative orientation of H-bonding interactions. The second strategy increased H-bonding interactions by introducing external H-donors onto analogs' backbone.