Inhibitors of Metabolic Pathways

One potential target of antibiotics can be reactions for the synthesis of metabolites such as nucleotides that are needed for the synthesis of DNA or RNA. The antibiotics that inhibit the synthesis of metabolites are compounds that resemble a certain metabolite and interferes with the normal metabolism involving that metabolite. Creative Biolabs provides the development of new inhibitors of metabolic pathways in high-quality. New antibiotics are produced in our state-of-the-art design platforms and through expertise in chemistries.

Antibiotics that Inhibit Folate Metabolism

The sulfa drugs, which include the sulfonamides, function by inhibiting folic acid biosynthesis in bacteria. Sulfa drugs are broad-spectrum bacteriostatic antibiotics because folic acid synthesis is essential for all species of bacteria. Human cells are not affected since they do not synthesize folic acid. Sulfa antibiotics have two main structural features. (1) All sulfa antibiotics have a free aminobenzene ring (N4) in the para position of their sulfonyl group. (2) Sulfonamide antibiotics usually contain a 5- or 6-membered nitrogen-containing ring attached to the sulfonylamino (N1).

The structure of sulfonamide resembles that of para-aminobenzoic acid (PABA), which is a precursor and integral part of the structure of folic acid. Folic acid (DHF) is synthesized in two stages. First, PABA reacts with a pteridine derivative to form dihydropteroic acid. This is followed by reaction with glutamic acid. Sulfonamide antibiotics function by inhibiting the enzyme dihydropteroate synthase (DHPS) which catalyzes the reaction of PABA with dihydropterin pyrophosphate to form dihydropteroate. Because of the similarity in structure, PABA and sulfonamides compete for binding to the active site of the enzyme.

Services

Based on structural information, Creative Biolabs provides three main methods to assist in the identification of new inhibitors of metabolic pathways.

• In the first approach, termed ‘substrate- and known inhibitor-inspired design’, the structures of sulfonamides, known inhibitors for the DHPS are modified to become inhibitors by maximizing complementary interactions in the target site.
• In the second approach, databases containing the structures of small molecules are docked into a region of interest in silico and scored according to their predicted interactions in the target site.
• The third approach involves the de novo design of inhibitor scaffolds. Fragments of molecules are positioned in chosen sites in the DHPS and then linked in silico to give complete molecules. These molecules can then be scored and ranked for factors such as their predicted binding affinity, their molecular complexity or their expected synthetic accessibility.

Creative Biolabs has focused on the development of new antibiotics for years, we whole-heartedly cooperate with you to accomplish our shared goals. Our team provides you with outstanding support and meets your specific needs with a professional technology platform. If you are interested in our services, please contact us for more details.

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