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Antibiotic resistance caused by biofilm formation is a clinical challenge. Nitric oxide (NO) can effectively disperse a mature biofilm and can also synergistically influence the level of cyclic diguanylate (c-di-GMP), a universal secondary messenger that plays an important role in biofilm formation in bacteria. Based on our previous finding that c-di-GMP G-quadruplex inducers are effective biofilm formation inhibitors, we designed and synthesized a c-di-GMP G-quadruplex inducer-NO donor conjugate (A11@NO) as a bifunctional antibiofilm agent after obtaining the c-di-GMP G-quadruplex inducer (A11), which has an amino group capable of binding to a nitroso group (NO donor). The conjugate A11@NOshowed better biofilm inhibition efficiency than A11, and it can also eradicate mature biofilm. Additionally, it exhibited good antimicrobial synergism against Pseudomonas aeruginosaand helped elevate the bactericidal efficiency of tobramycin against biofilm-formed bacteria. In combination with tobramycin, A11@NOalso improved the survival rate of Caenorhabditis elegansin a hyperbiofilm environment.

The ghrelin receptor, also known as the growth hormone secretagogue receptor 1a (GHS-R1a), is a G-protein coupled receptor that is differentially expressed in healthy tissue and several cancers, including prostate, testicular, and ovarian. Selectively targeting the ghrelin receptor using fluorine-18 tagged entities would allow localization and visualization of ghrelin receptor expressing carcinomas using PET imaging. The endogenous ligand ghrelin, a 28 amino acid peptide with 3.1 nM affinity, has poor in vivo stability. Here we report on ghrelin(1-8) analogues bearing modifications at residues 1, 3, 4, and 8. The lead analogue, [Inp1,Dpr3(6-fluoro-2-naphthoate),1-Nal4,Thr8]ghrelin(1-8), possessed an IC50value of 0.11 nM that is a 28-fold improvement compared to the natural ligand. A novel 6-fluoro-2-pentafluorophenyl naphthoate (PFPN) prosthetic group was synthesized to incorporate fluorine-18 for PET imaging. This is not only the highest affinity ghrelin analogue reported, it is also the shortest ghrelin analogue capable of binding GHS-R1a with better affinity than ghrelin(1-28).