Biological ligands are molecules that bind specifically to a target molecule, typically a larger protein. This interaction can regulate the protein’s function or activity in various biological processes. Ligands can be of different types, including small molecules, peptides, nucleotides, and others. In biochemistry and pharmacology, understanding ligands and their interactions with proteins is crucial for drug design and for understanding cellular signalling pathway
Biological ligands can interact with a variety of molecular targets in the body, each playing a critical role in influencing physiological processes. Ligands can activate or inhibit enzymes, which are proteins that catalyze biochemical reactions. For example, many drugs act as enzyme inhibitors to slow down or halt specific metabolic pathways that contribute to disease.
Ion Channels are pore-forming proteins that help establish and control voltages across cell membranes by allowing the flow of ions in and out of the cell. Ligands can modulate ion channels by opening or closing them, altering cellular activity. G Protein-Coupled Receptors (GPCRs) are large and diverse group of receptors which detect molecules outside the cell and activates internal signal transduction pathways and cellular responses. Many hormones and neurotransmitters operate through GPCRs.
Nuclear Receptors reside within a cell and directly interact with DNA to regulate the expression of specific genes. Ligands for these receptors often include steroid hormones and fat-soluble vitamins. Transporters are proteins that move molecules across cellular membranes. Ligands can influence the function of transporters to modulate the uptake or expulsion of crucial metabolites, drugs, or toxins. While less common, some ligands can directly interact with ribosomal subunits, influencing protein synthesis. Certain antibiotics work by targeting bacterial ribosomes, thus inhibiting bacterial protein production.
Understanding the interaction between ligands and their molecular targets is crucial for drug development and for comprehending cellular and physiological mechanisms.
Ligands, especially in a biochemical context, often contain specific functional groups that enable them to bind to their molecular targets with high affinity and specificity. Functional groups are particular groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. Here are some common functional groups found in biological ligands and their roles:
1. Hydroxyl Group (-OH): Found in alcohols and many biomolecules like carbohydrates and steroids, hydroxyl groups can form hydrogen bonds with amino acids in the active site of enzymes or receptors, enhancing solubility and reactivity.
2. Carboxyl Group (-COOH): This group is common in amino acids, fatty acids, and other organic acids. It can donate a proton and thus act as an acid, making it crucial for interactions in enzymatic and receptor binding sites.
3. Amino Group (-NH2): Present in amino acids and many neurotransmitters, amino groups can act as bases and form hydrogen bonds or ionic bonds with their targets, contributing to binding stability and specificity.
4. Phosphate Group (-PO4): A key group in nucleotides and many signaling molecules (like ATP), phosphate groups are highly polar and can participate in multiple hydrogen bonds and ionic interactions, important for binding to proteins like kinases and phosphatases.
5. Sulfhydryl Group (-SH): Found in molecules like cysteine, sulfhydryl groups can form disulfide bonds that are crucial for the structural stability of proteins and for ligand-protein interactions.
6. Aldehyde and Ketone Groups (C=O): These carbonyl groups are polar and can participate in hydrogen bonding. They’re central in many biochemical reactions and can influence ligand binding through these interactions.
7. Aromatic Rings: Structures like benzene rings, found in many drugs and signaling molecules, can participate in π-π interactions and hydrophobic interactions, crucial for binding to hydrophobic pockets within proteins.
Each functional group contributes distinct chemical properties to a ligand, influencing how it interacts with its biological target. Understanding these interactions is vital for designing new therapeutic agents and for elucidating mechanisms of action at a molecular level.
The similarity in functional groups between biological ligands and pathogenic molecules can play a significant role in disease processes, particularly in how pathogens exploit host cellular mechanisms or evade the immune system. This molecular mimicry, where pathogenic molecules share structural features with host molecules, can lead to various effects, including immune evasion, autoimmune reactions, and altered cellular signaling. Here’s how these similarities can influence disease processes:
Pathogens often mimic host molecules to evade the immune system. For instance, some bacteria express surface proteins with functional groups similar to those found in the host’s tissues, allowing them to blend in and avoid detection by immune cells. When pathogens mimic host molecules too closely, the immune system may develop antibodies or T-cell receptors that react not only against the pathogen but also against the host’s own cells. This molecular mimicry is a known mechanism in the development of autoimmune diseases. For example, the similarity between certain viral proteins and myocardial or pancreatic beta cell antigens can lead to autoimmune reactions against the heart or pancreas.
Pathogenic molecules may mimic the functional groups of endogenous ligands, allowing them to bind to host receptors and either activate them inappropriately or block their normal function. This can disrupt normal cellular signalling and contribute to disease. For example, bacterial toxins often mimic neurotransmitters or hormones, binding to their receptors and causing overstimulation or inhibition of cellular functions. By sharing functional groups with physiological ligands, pathogenic molecules can interfere with normal biochemical pathways. This interference can alter crucial metabolic or signaling pathways, leading to disease symptoms. For example, some viral proteins mimic host enzymes or co-factors and can disrupt metabolic pathways or DNA replication processes.
Understanding the similarity in functional groups also aids in drug development, where therapeutic agents are designed to specifically target pathogenic molecules mimicking host molecules, aiming to block their harmful interactions without affecting the host’s normal physiological processes. The role of similarity in functional groups between biological ligands and pathogenic molecules is a double-edged sword in disease processes, contributing both to pathogenic mechanisms and therapeutic opportunities.
According to MIT homeopathic perspective, biological ligands potentized above 12 c will contain molecular imprints of constituent functional groups. Molecular imprints of drugs that compete with natural biological ligands for same biological targets also could be used, as both of their functional groups will be similar. These molecular imprints could be used as artificial binding pockets to deactivate any pathogenic molecule that create biomolecular inhibitions by binding to the biological target molecules by their functional groups. As per this approach, therapeutics involves identifying the biological ligands implicated in a particular disease condition, preparing their molecular imprints by homeopathic potentization, and administering those molecular imprints as disease-specific formulations.
BIOLOGICAL LIGANDS AND THEIR FUNCTIONAL GROUPS
1. Ligand: Acetylcholine
Functional groups: Ester (acetyl + choline)
Molecular Targets: Acetylcholine receptors
Biological Roles: Neurotransmitter in CNS and PNS
Competing drugs: Atropine, scopolamine
2. Ligand: Adrenaline
Functional groups: Catechol, amine
Molecular Targets: Adrenergic receptors
Biological Roles: Fight-or-flight response
Competing drugs: Propranolol, metoprolol
3. Ligand: Estrogen
Functional groups: Phenolic, hydroxyl, ketone
Molecular Targets: Estrogen receptor
Biological Roles: Regulation of reproductive system
Competing drugs: Tamoxifen, raloxifene
4. Ligand: Glucose
Functional groups: Aldehyde, hydroxyl
Molecular Targets: Glucose transporters
Biological Roles: Primary energy source
Competing drugs: Phlorizin
5. Ligand: Cortisol
Functional groups: Ketone, hydroxyl
Molecular Targets: Glucocorticoid receptor
Biological Roles: Stress response, metabolism regulation
Competing drugs: Mifepriston
6. Ligand: Insulin
Functional groups: Peptide (amino acids)
Molecular Targets: Insulin receptor
Biological Roles: Regulation of glucose uptake
Competing drugs: Synthetic insulins (e.g., lispro, aspart)
7. Ligand: Nitric oxide
Functional groups: Nitric oxide (NO)
Molecular Targets: Guanylate cyclase
Biological Roles: Vasodilation, neurotransmission
Competing drugs: Sildenafil, tadalafil
8. Ligand: Dopamine
Functional groups: Catechol, amine
Molecular Targets: Dopamine receptors
Biological Roles: Reward, pleasure, motor function
Competing drugs: Haloperidol, chlorpromazine
9. Ligand: Retinoic acid
Functional groups: Carboxylic acid
Molecular Targets: Retinoic acid receptors
Biological Roles: Cell differentiation and growth
Competing drugs: Bexarotene, tretinoin
10. Ligand: Vitamin D
Functional groups: Hydroxyl, secosteroid
Molecular Targets: Vitamin D receptor
Biological Roles: Calcium homeostasis, bone remodeling
Competing drugs: Calcipotriene
11. Ligand: Serotonin,
Functional groups: Amino, indole,
Molecular Targets: Serotonin receptors,
Biological Roles: Mood regulation, digestion, sleep,
Competing drugs: Ondansetron, fluoxetine
12. Ligand: GABA,
Functional groups: Amino, carboxylic acid,
Molecular Targets: GABA receptors,
Biological Roles: Inhibitory neurotransmitter in CNS,
Competing drugs: Benzodiazepines, barbiturates
13. Ligand: Testosterone,
Functional groups: Keto, hydroxyl,
Molecular Targets: Androgen receptor,
Biological Roles: Male sexual development, muscle growth,
Competing drugs: Flutamide, bicalutamide
14. Ligand: (T4),
Functional groups: Amino, iodine, phenolic,
Molecular Targets: Thyroid hormone receptor
Biological Roles: Metabolism regulation, growth and development,
Competing drugs: Levothyroxine (synthetic T4)
15. Ligand: Folic acid,
Functional groups: Pteridine, glutamate, para-aminobenzoic acid,
Molecular Targets: Dihydrofolate reductase,
Biological Roles: DNA synthesis, cell division,
Competing drugs: Methotrexate
16. Ligand: Oxytocin,
Functional groups: Peptide (amino acids),
Molecular Targets: Oxytocin receptor,
Biological Roles: Social bonding, childbirth, lactation,
Competing drugs: Atosiban
17. Ligand: Leptin,
Functional groups: Peptide (amino acids),
Molecular Targets: Leptin receptor,
Biological Roles: Appetite regulation, energy expenditure,
Competing drugs: Synthetic leptin analogs
18. Ligand: Norepinephrine,
Functional groups: Catechol, amine,
Molecular Targets: Adrenergic receptors,
Biological Roles: Attention, stress response, heart rate control,
Competing drugs: Phenoxybenzamine, prazosin
19. Ligand: Progesterone,
Functional groups: Keto, hydroxyl,
Molecular Targets: Progesterone receptor,
Biological Roles: Menstrual cycle, pregnancy maintenance,
Competing drugs: Mifepristone, ulipristal acetate
20. Ligand: Histamine,
Functional groups: Imidazole, amine,
Molecular Targets: Histamine receptors,
Biological Roles: Immune response, gastric secretion, sleep,
Cetirizine, ranitidine
21. Ligand: Melatonin,
Functional groups: Amino, acetyl,
Molecular Targets: methoxy,Melatonin receptors,
Biological Roles: Sleep-wake cycle regulation,
Competing drugs: Ramelteon, agomelatine
22. Ligand: Aldosterone,
Functional groups: Keto, aldehyde,
Molecular Targets: Mineralocorticoid receptor,
Biological Roles: Electrolyte and water balance,
Competing drugs: Spironolactone, eplerenone
23. Ligand: Epinephrine,
Functional groups: Catechol, amine,
Molecular Targets: Adrenergic receptors
Biological Roles: Cardiovascular control, anaphylaxis response,
Competing drugs: Epinephrine antagonists
24. Ligand: Thyroid Stimulating Hormone (TSH),
Functional groups: Glycoprotein,
Molecular Targets: TSH receptor,
Biological Roles: Thyroid gland stimulation,
Competing drugs: Recombinant TSH (Thyrotropin)
25. Ligand: Calcitonin,
Functional groups: Peptide (amino acids),
Molecular Targets: Calcitonin receptor,
Biological Roles: Bone resorption and calcium homeostasis,
Competing drugs: Calcitonin-salmon
26. Ligand: Endorphins,
Functional groups: Peptide (amino acids),
Molecular Targets: Opioid receptors,
Biological Roles: Pain relief, pleasure sensation,
Competing drugs: Naloxone, naltrexone
27. Ligand: Angiotensin II,
Functional groups: Peptide (amino acids),
Molecular Targets: Angiotensin II receptors,
Biological Roles: Blood pressure regulation, fluid balance,
Competing drugs: Losartan, valsartan
28. Ligand: Bradykinin,
Functional groups: Peptide (amino acids),
Molecular Targets: Bradykinin receptors,
Biological Roles: Inflammatory response, vasodilation,
Competing drugs: Icatibant, bradykinin antagonists
29. Ligand: Atrial Natriuretic Peptide (ANP),
Functional groups: Peptide (amino acids),
Molecular Targets: ANP receptors,
Biological Roles: Sodium excretion, lowers blood pressure,
Competing drugs: Nesiritide (synthetic ANP)
30. Ligand: Substance P,
Functional groups: Peptide (amino acids),
Molecular Targets: Neurokinin receptors,
Biological Roles: Pain transmission, stress response,
Competing drugs: Aprepitant, fosaprepitant
31. Ligand: Insulin-like Growth Factor 1 (IGF-1) –
Functional groups: Peptide:
Molecular Targets: IGF-1 receptor,
Biological Roles: Growth and development,
Competing drugs: Mecasermin
32. Ligand: Somatostatin –
Functional groups: Peptide:
Molecular Targets: Somatostatin receptors,
Biological Roles: Inhibit growth hormone release,
Competing drugs: Octreotide
33. Ligand: Corticotropin-Releasing Hormone (CRH) –
Functional groups: Peptide:
Molecular Targets: CRH receptor,
Biological Roles: Stress response,
Competing drugs: Antalarmin
34. Ligand: Gastrin –
Functional groups: Peptide:
Molecular Targets: Gastrin/CCK-B receptor,
Biological Roles: Stimulates gastric acid secretion,
Competing drugs: Proglumide
35. Ligand: Cholecystokinin (CCK) –
Functional groups: Peptide:
Molecular Targets: CCK receptors,
Biological Roles: Digestive enzyme secretion, gastrointestinal motility,
Competing drugs: Devazepide
36. Ligand: Secretin – ml
Functional groups: Peptide:
Molecular Targets: Secretin receptor,
Biological Roles: Regulates water homeostasis and bicarbonate secretion,
Secretin (synthetic)
37. Ligand: Ghrelin –
Functional groups: Peptide:
Molecular Targets: Growth hormone secretagogue receptor, Stimulates appetite, Biological Roles: Growth hormone release,
Competing drugs: Netazepide
38. Ligand: Vasopressin –
Functional groups: Peptide:
Molecular Targets: Vasopressin receptors,
Biological Roles: Water retention, vasoconstriction,
Competing drugs: Conivaptan
39. Ligand: Orexin –
Functional groups: Peptide:
Molecular Targets: Orexin receptors,
Biological Roles: Regulates arousal, wakefulness, and appetite,
Competing drugs: Suvorexant
40. Ligand: Prolactin –
Functional groups: Peptide:
Molecular Targets: Prolactin receptor,
Biological Roles: Lactation,
Competing drugs: Bromocriptine
41. Ligand: Thrombopoietin –
Functional groups: Peptide:
Molecular Targets: MPL receptor,
Biological Roles: Platelet production,
Competing drugs: Eltrombopag
42. Ligand: Erythropoietin (EPO) –
Functional groups: Glycoprotein:
Molecular Targets: EPO receptor,
Biological Roles: Red blood cell production,
Competing drugs: Epoetin alfa
43. Ligand: Glucagon –
Functional groups: Peptide:
Molecular Targets: Glucagon receptor,
Biological Roles: Raises blood glucose levels,
Competing drugs: Glucagon (synthetic)
44. Ligand: Growth Hormone (GH) –
Functional groups: Protein:
Molecular Targets: Growth hormone receptor,
Biological Roles: Growth promotion,
Competing drugs: Somatropin
45. Ligand: Parathyroid Hormone (PTH) –
Functional groups: Peptide:
Molecular Targets: PTH receptor,
Biological Roles: Calcium and phosphate metabolism,
Competing drugs: Teriparatide
46. Ligand: Calcitriol (Vitamin D3) –
Functional groups: Secosteroid:
Molecular Targets: Vitamin D receptor,
Biological Roles: Calcium absorption,
Calcitriol (synthetic)
47. Ligand: Triiodothyronine (T3) –
Functional groups: Amino acid derivative:
Molecular Targets: Thyroid hormone receptor,
Biological Roles: Metabolic regulation,
Competing drugs: Liothyronine
48. Ligand: Neurotensin –
Functional groups: Peptide:
Molecular Targets: Neurotensin receptors,
Biological Roles: Pain modulation, gastrointestinal function,
Competing drugs: SR 48692
49. Ligand: Motilin –
Functional groups: Peptide:
Molecular Targets: Motilin receptor,
Biological Roles: Gastric motility,
Competing drugs: Erythromycin
50. Ligand: Luteinizing Hormone (LH) –
Functional groups: Glycoprotein:
Molecular Targets: LH receptor,
Biological Roles: Regulates reproductive system,
Competing drugs: Lutropin alfa
51. Ligand: Follicle-stimulating Hormone (FSH) –
Functional groups: Glycoprotein:
Molecular Targets: FSH receptor,
Biological Roles: Reproductive system regulation,
Competing drugs: Follitropin alfa/beta
52. Ligand: Vasopressin (ADH) –
Functional groups: Peptide:
Molecular Targets: V1a and V2 receptors,
Biological Roles: Water retention, blood pressure regulation,
Competing drugs: Desmopressin
53. Ligand: Bile Acids –
Functional groups: Steroids:
Molecular Targets: FXR receptor,
Biological Roles: Fat digestion and cholesterol regulation,
Competing drugs:
54. Ligand: Amylin –
Functional groups: Peptide:
Molecular Targets: Amylin receptor,
Biological Roles: Modulates gastric emptying, glucagon secretion,
Competing drugs: Pramlintide
55. Ligand: Glucagon-like Peptide-1 (GLP-1) –
Functional groups: Peptide:
Molecular Targets: GLP-1 receptor,
Biological Roles: Enhances insulin secretion,
Competing drugs: Exenatide, Liraglutide
56. Ligand: Catestatin –
Functional groups: Peptide:
Molecular Targets: Nicotinic acetylcholine receptors,
Biological Roles: Modulates cardiovascular function,
Competing drugs: No direct drugs but related to nicotinic antagonists.
57. Ligand: Angiotensin I –
Functional groups: Peptide:
Molecular Targets: Converted to Angiotensin II by ACE,
Biological Roles: Precursor to active peptide,
Competing drugs: ACE inhibitors (e.g., Lisinopril).
58. Ligand: Endothelin-1 –
Functional groups: Peptide:
Molecular Targets: Endothelin receptors,
Biological Roles: Vasoconstriction,
Competing drugs: Bosentan, Ambrisentan.
59. Ligand: Renin –
Functional groups: Aspartic protease:
Molecular Targets: Renin receptors,
Biological Roles: Regulates blood pressure via RAAS,
Competing drugs: Aliskiren.
60. Ligand: Interleukin-1 (IL-1) –
Functional groups: Protein:
Molecular Targets: IL-1 receptors,
Biological Roles: Immune response modulation,
Competing drugs: Anakinra.
61. Ligand: Interleukin-6 (IL-6) –
Functional groups: Glycoprotein:
Molecular Targets: IL-6 receptor,
Biological Roles: Inflammatory and immune response,
Competing drugs: Tocilizumab.
62. Ligand: Tumor Necrosis Factor (TNF) –
Functional groups: Protein:
Molecular Targets: TNF receptors,
Biological Roles: Regulation of immune cells,
Competing drugs: Infliximab.
63. Ligand: Transforming Growth Factor-beta (TGF-β) –
Functional groups: Protein:
Molecular Targets: TGF-β receptors,
Biological Roles: Cell growth and differentiation,
Competing drugs: Galunisertib.
64. Ligand: Vascular Endothelial Growth Factor (VEGF) –
Functional groups: Protein:
Molecular Targets: VEGF receptors,
Biological Roles: Angiogenesis,
Competing drugs: Bevacizumab.
65. Ligand: Interferon-gamma (IFN-γ) –
Functional groups: Protein:
Molecular Targets: IFN-γ receptors,
Biological Roles: Immune response against pathogens,
Competing drugs: direct competing drugs; used as therapeutic itself.
66. Ligand: Interferon-alpha (IFN-α) –
Functional groups: Protein:
Molecular Targets: IFN-α receptors,
Biological Roles: Antiviral responses,
Competing drugs: Peginterferon alfa-2a.
67. Ligand: Brain-Derived Neurotrophic Factor (BDNF) –
Functional groups: Protein:
Molecular Targets: TrkB receptor,
Biological Roles: Neuronal survival and growth,
Competing drugs: No direct competing drugs; research focus.
68. Ligand: Fibroblast Growth Factor (FGF) –
Functional groups: Protein:
Molecular Targets: FGF receptors,
Biological Roles: Tissue repair, cell growth,
Competing drugs: Dovitinib.
69. Ligand: Leukotriene B4 (LTB4) –
Functional groups: Eicosanoid:
Molecular Targets: LTB4 receptor,
Biological Roles: Inflammatory response,
Competing drugs: Montelukast.
70. Ligand: Prostaglandin E2 (PGE2) –
Functional groups: Eicosanoid:
Molecular Targets: Prostaglandin receptors,
Biological Roles: Inflammation and pain,
Competing drugs: NSAIDs like Ibuprofen.
71. Ligand: Sphingosine-1-phosphate (S1P) –
Functional groups: Lipid:
Molecular Targets: S1P receptors,
Biological Roles: Immune cell trafficking,
Competing drugs: Fingolimod.
72. Ligand: Corticotropin (ACTH) –
Functional groups: Peptide:
Molecular Targets: Melanocortin receptors,
Biological Roles: Stimulates cortisol production,
Competing drugs: No direct competitors; synthetic ACTH used for diagnostic.
73. Ligand: Neuropeptide Y (NPY) –
Functional groups: Peptide:
Molecular Targets: NPY receptors,
Biological Roles: Appetite regulation, stress response,
Competing drugs: No direct competing drugs; research focus.
74. Ligand: Somatocrinin (GHRH) –
Functional groups: Peptide:
Molecular Targets: GHRH receptors,
Biological Roles: Stimulates GH release,
Competing drugs: Sermorelin.
75. Ligand: Kisspeptin –
Functional groups: Peptide:
Molecular Targets: Kisspeptin receptor,
Biological Roles: Regulates hormone secretion related to reproduction,
Competing drugs: No direct competing drugs; research focus.
76. Ligand: Relaxin –
Functional groups: Peptide:
Molecular Targets: RXFP1 receptor,
Biological Roles: Pregnancy-related changes in tissues,
Competing drugs: No widely used competing drugs
77. Ligand: Adiponectin –
Functional groups: Protein:
Molecular Targets: AdipoR1 and AdipoR2 receptors,
Biological Roles: Glucose regulation and fatty acid breakdown,
Competing drugs: No direct competing drugs; research focus.
78. Ligand: Gastric Inhibitory Polypeptide (GIP) –
Functional groups: Peptide:
Molecular Targets: GIP receptors,
Biological Roles: Inhibits gastric acid secretion, enhances insulin release,
Competing drugs: No direct competing drugs; research on GLP-1 analogues overlaps.
79. Ligand: Urocortin –
Functional groups: Peptide:
Molecular Targets: CRF receptors,
Biological Roles: Stress response,
Competing drugs: No direct competing drugs; research focus.
80. Ligand: Matrix Metalloproteinases (MMPs) –
Functional groups: Enzyme:
Molecular Targets: Tissue matrix,Biological Roles: Tissue remodeling, Cancer metastasis,
Competing drugs: Marimastat.
REDEFINING HOMEOPATHY 