Sulfamethoxazole

For the past 70 years, antibiotics drugs have successfully treated patients with infections. But over time, some bacteria have developed resistance to antibiotics that were once commonly used to treat them and have caused serious disease, thus, antibiotic resistance has become one of the biggest public health challenges all over the world. Currently, antibody-antibiotic conjugate (AAC) emerges as a promising treatment approach for antibiotic-resistant bacteria infection. Based on years of extensive experience in antibody-drug conjugates (ADCs) development and manufacture, Creative Biolabs can offer a full range of high-quality AACs services use sulfamethoxazole as payloads for bacterial infection therapy. With the help of our professional scientists, we are confident in providing unique services to meet every customer's requirements.

Introduction

Sulfamethoxazole (SMZ or SMX) antibiotic is used for the treatment of bacterial infections such as urinary tract infections, bronchitis, and prostatitis, and is potent against both gram negative and positive bacteria such as Listeria monocytogenes and E. coli. It was approved in the United States in 1961. At present, it is mostly used in combination with trimethoprim (abbreviated SMX-TMP). It is also referred to sulfamethalazole, sulfisomezole, and sulfamethazole.

Fig.1 The chemical structure of sulfamethoxazole (3-Sulfanilamido-5-methylisoxazole). (DrugBank, 2015)

Mode of Action of Sulfamethoxazole
Sulfamethoxazole is a sulfanilamide, and structural analog of para-aminobenzoic acid (PABA). They can hinder the transformation of PABA and dihydropteroate diphosphate to dihydrofolic acid, or dihydrofolate by competing with PABA to bind to dihydropteroate synthetase. Therefore, this inhibits the production of dihydrofolate intermediate interferes with the normal synthesis of folic acid (folate) of bacteria. However, folate is a critical metabolite for bacterial growth and replication since it is needed in DNA synthesis, especially at thymidylate and purine biosynthesis, and amino acids synthesis, including serine, glycine and methionine. As a consequence, blockage of folate production restrains the folate-dependent metabolic processes for bacterial growth. Due to its ability in inhibiting bacterial growth, sulfamethoxazole is considered as a bacteriostatic antibiotic.

Fig.2 Sulfonamides inhibit conversion of PABA and dihydropteroate diphosphate to dihydrofolic acid or dihydrofolate.

Sulfamethoxazole-based AACs

Here the sulfamethoxazole as payloads is used in AACs to achieve the goal to kill antibiotic-resistant bacteria. The AAC uses the antibody to deliver the antibiotic payload to bacteria. The monoclonal antibodies possess the specific targeting capability to deliver sulfamethoxazole exclusively to the infection site, thereby decreasing collateral damage to the normal tissues.Upon mAbs recognizing the antigen of bacteria, AAC complex is internalized via receptor-mediated endocytosis and the potent sulfamethoxazole payload is released to accomplish its cytotoxic effects. In addition, during therapeutic applications, the AAC displays advantages including specificity, safety, and stability to achieve effective delivery of the payload to the target.

Creative Biolabs is one of the well-recognized experts in applying ADC design and development services against all kinds of diseases. At present, we provide high-quality AAC development using sulfamethoxazole as the drug in a cost-effective manner. With years of experience, our scientists can offer high-quality AACs development services to meet our customers’ demands. Please feel free to contact us.

References

1. "Sulfamethoxazole". DrugBank. Retrieved 5 November 2015.