Switching the Chemoselectivity in the Preparation of [F]FNA--CooP, a Free Thiol-Containing Peptide for Targeted Positron Emission Tomography Imaging of Fatty Acid Binding Protein 3.

Fatty acid binding protein 3 (FABP3) is expressed both in tumor cells and in the tumor vasculature, making it a potential target for medical imaging and therapy. In this study, we aimed to radiolabel a CooP peptide with a free amino and thiol group, and evaluate the radiolabeled product [F]FNA--CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [F]FNA--CooP was prepared by highly chemoselective -acylation and characterized using different chemical approaches.

Radiosynthesis, structural identification and in vitro tissue binding study of [F]FNA-S-ACooP, a novel radiopeptide for targeted PET imaging of fatty acid binding protein 3.

Background: Fatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (F) for positron emission tomography (PET) applications, and evaluate the binding of the radiolabeled ACooP in human tumor tissue sections with high FABP3 expression.

Solid-phase synthesis of 4(5),1',5'-trisubstituted 2,4'-biimidazoles.

A method for the synthesis of libraries of 4(5),1',5'-trisubstituted 2,4'-biimidazoles on a solid support was developed. (1) A trivalent scaffold, 2-(5'-amino-4(5)-formyl-1H,1'H-2,4'-biimidazol-1'-yl)acetic acid, was first prepared in solution by a two-step synthesis from ethyl adenin-9-ylacetate and bromomalonaldehyde. The product was coupled to an amino acid loaded Wang resin and the formyl group was subsequently derivatized either by reductive amination, oximation, or hydrazone formation.

Solid-phase synthesis of 7-substituted 3H-imidazo[2,1-i]purines.

A method for solid-supported synthesis of N,N-disubstituted (3H-imidazo[2,1-i]purin-7-yl)methyl amines has been developed. The key features of this library synthesis are: (i) immobilization of commercially available N6-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine 3'-(2-cyanoethyl N,N-diisopropylphosphoramidite) by phosphitylation to a hydroxyl-functionalized support, (ii) quantitative conversion of the deprotected adenine base to 3H-imidazo[2,1-i]purine-7-carbaldehyde with bromomalonaldehyde in DMF in the presence of formic acid and 2,6-lutidine, (iii) reductive amination of the formyl group followed by N-alkylation or N-acylation, and (iv) release from the support by acidolytic cleavage of the N-glycosidic bond. Steps (ii) and (iii) have been optimized in some detail by using (adenin-9-yl)acetic acid anchored to a Phe-Wang resin as a model compound.

An Orthogonally Protected alpha,alpha-bis(aminomethyl)-beta-alanine building block for the construction of glycoconjugates on a solid support.

Synthetic glycoclusters are extensively used as mimetics of naturally occurring, multivalent carbohydrate ligands in various glycobiological applications. Their preparation, however, is far from trivial, and it still is a limiting factor in the study of carbohydrate binding. We herein report the synthesis of an orthogonally protected building block, N-Alloc-N'-Boc-N' '-Fmoc-alpha,alpha-bis(aminomethyl)-beta-alanine (1), and its use in the preparation of triantennary peptide glycoclusters (21-24) on a solid support.

Improving broad specificity hapten recognition with protein engineering.

Sulfa antibiotics (sulfonamides) are derivatives of p-aminobenzenesulfonamide that are widely used in veterinary medicine. Foods derived from treated animals may be contaminated with these drugs. However, current immunobased sulfonamide detection methods are unfit for screening of products because they are either too insensitive or specific for a few compounds only.