Medical Chemistry

Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Surface receptors are bound to the cell membrane, receive signals from their surrounding environment, and transmit those signals into the cell, often via the generation of 2nd messengers (like cyclic adenosine monophosphate (cAMP)) or through phosphorylation cascades. There are multiple different subclasses of surface receptors, and 3 of the most important classes include ligand-gated ion channel receptors, enzyme-linked receptors (the most common of which are receptor tyrosine kinases (RTKs)), and G-protein-coupled receptors (GPCRs). Intracellular receptors, on the other hand, are located within the cytoplasm and often act as transcription factors, directly interacting with DNA and affecting gene expression.

Proteins are 1 of the 3 primary macronutrients in the body and are synthesized from individual building blocks called amino acids (AAs). Amino acids are bound together by peptide bonds, which link the amino end of one AA to the carboxy end of the next AA, generating a protein's primary structure. The strand of AAs then undergoes additional folding, ultimately generating complex 3-dimensional structures. Proteins have a wide variety of functions, including catalytic, structural, regulatory, transport, storage, and immunologic functions. They are digested by proteases and peptidases secreted by the stomach and pancreas and absorbed as individual AAs in the small intestines through specialized transporters. There are countless medical conditions related to protein abnormalities, including abnormalities related to enzymes, receptors, membrane channels, hormones, accumulation of proteins, and autoimmune disorders.

Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Another way to describe the difference between the 2 disciplines is to say that pharmacokinetics is "what the body does to the drug," whereas pharmacodynamics is "what the drug does to the body." When prescribing medications, physicians must take into account both the drug's pharmacodynamics and its pharmacokinetics to determine the correct dosage and to ensure the appropriate effect.

Enzyme inhibitors bind to enzymes and decrease their activity. Enzyme activators bind to enzymes and increase their activity. Molecules that decrease the catalytic activity of enzymes can come in various forms, including reversible or irreversible inhibition. Reversible inhibition can be competitive, non-competitive, or uncompetitive.

Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Beta-lactam antibiotics block bacterial transpeptidase (penicillin-binding protein) and, therefore, inactivate peptidoglycan crosslinking in the cell wall. All beta-lactam antibiotics are bactericidal. Common mechanisms of resistance include beta-lactamase production or mutation in the penicillin-binding protein gene. The common side effects include hypersensitivity reactions, GI upset, and hemolytic anemia.

Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins have expanded antimicrobial activity compared with most penicillins, and are more effective against Enterobacteriaceae; some drugs are active against Pseudomonas and/or anaerobic species as well. Cephalosporins are often used to treat skin, soft tissue, bone, lung, urinary tract, intraabdominal, and pelvic infections caused by susceptible organisms.

The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. There are 4 available carbapenems, all ending in “-penem,” and 1 available monobactam, which is aztreonam. The carbapenems are all broad-spectrum antibiotics used for a variety of serious, often MDR and/or hospital-acquired infections (HAIs) that can occur throughout the body. Aztreonam has a narrower spectrum and is typically used for aerobic gram-negative bacilli infections in patients who have a serious beta-lactam allergy but require beta-lactam therapy, as there is no significant cross-allergenicity between aztreonam and the other beta-lactams.

Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). There are hundreds of AAs found in nature, but only 20 are the building blocks of proteins in humans (proteinogenic). Nine of these 20 are “essential,” as they cannot be synthesized. Amino acids differ from one another only in the chemical nature of the R group. They are most commonly classified according to their interaction with water as hydrophobic, hyd

Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Enzymes have many functions, including macromolecule degradation and synthesis (catabolism and anabolism), signal transduction, energy generation (adenosine triphosphate [ATP]), ion pumps/active transport, defense and clearance reactions (oxidization, reduction, hydrolysis), cell regulation, movement (myosin ATPase, transport of intracellular substances), and immune responses.

Prodrugs are the derivatives of active drug molecules. They must undergo an enzymatic and/or chemical transformation in-vivo to be converted into the active form. Prodrugs are utilized to improve the physicochemical, pharmacokinetic, and pharmacodynamic properties of compounds. This article discusses the concept of prodrugs, their common properties, and the most common scenarios where they are likely to be utilized.

Drug and receptor interaction is an important field of study in medicine. Knowing the chemistry behind these interactions helps in understanding a drug’s mechanism and efficacy in the treatment of a disease. This article will discuss the structural basis of the receptors found in biological membranes, as well as differentiate the various types of interactions possible between a drug and its receptor.