Review Article (Open access)

Int. J. Life. Sci. Scienti. Res., 4(3): 1780-1785, May 2018

Biological Scope of β-Amino Acids and its Derivatives in Medical Fields and Biochemistry

Fazal-ur-Rehman M*

Research Scholar, Department of Chemistry, University of Education, Lahore (Vehari Campus), Vehari- 61100, Punjab, Pakistan

*Address for Correspondence: Fazal-ur-Rehman M, Research Scholar, Department of Chemistry, University of Education, Lahore (Vehari Campus), Vehari- 61100, Punjab, Pakistan

 

ABSTRACT- Beta amino acids are the important macromolecules on earth and building blocks. They play a key role in biological systems of living organisms. They are utilized as a part of arrangement for the most part pharmaceuticals. They have huge part in human science. They have pharmaceutical properties like as hypoglycaemic, anti-ketogenic, antibacterial properties, antifungal exercises, and powerful insecticidal properties. They have pharmaceutical applications as they are utilized to get ready pharmaceutical items and agrochemical target atoms. Not just them, but their derivatives also play significant roles in different systems of organismal bodies. They also act as essential enzymes in humans as well as in animals. This review explores the scope of Beta amino acids.

Key words: β-amino acids, Neurotransmitter, Pharmaceuticals, Anti-toxins, Pharmaceutical

INTRODUCTION- β-Amino acids (β-AAc) are building fragments. [1] They are utilized as a part of arrangement of for the most part pharmaceuticals [2] and agrochemicals items. [3] Since they have critical properties as they are proteinogenic [4], non-proteinogenic properties. They have huge part in human science.[5] As they go about as neurotransmitter [6], biosynthesizer [7], and furthermore as healthful supplements materials.[8] They are likewise utilized as a part of natural amalgamation as impetus.[9] β-AAc has pharmaceutical properties like as hypoglycaemic [10-14], antiketogenic [15], antibacterial properties[16], antifungal exercises [17], powerful insecticidal properties [18]. They have found extensive applications as components of biologically active peptides and small molecule pharmaceuticals. Synthetic derivatives of biologically relevant peptides incorporating β-AAc often display interesting pharmacological activity, with increased potency and enzymatic stability. The β-peptides participate in arrangement of incredible stable auxiliary structures. They have pharmaceutical applications as they are utilized to get ready pharmaceutical items and agrochemical target atoms.[19]

They are constituents of numerous vital organic dynamic items [20] and in addition drugs. [21] Anti-toxins have auxiliary moieties of β-lactam.[22] β-peptides partake in arrangement of incredible stable optional structures. [23-27]

Applications of β-amino acids- β-peptides are exceptionally steady biomolecules in vitro and vivo proteolytic corruption. [28] They were utilized to plan anti-toxins as magainins[29] that were very intense. In any case, it was difficult to use it as basic medications because of corruption by proteolytic compounds in bodies. [30]

They assume vital part in direction of healthful digestion and invulnerability.[31] Arginine family amino acids (AFAA) is likewise essential in β-AAc. [32] There is inadequacy of Arginine in drain of a few warm blooded creatures like pigs. [33] AFAA is insufficient for most extreme fetal development.[34] AFAA is related with most extreme development of placenta[35] and amalgamation of polyamines [36] in start of pregnancy. Arginine is an antecedent of nitric oxide. Arginine is the forerunner of creatine (a vitality repository in our muscles,), nitrogen oxide (an arbiter of vein narrowing), citrulline (a cancer prevention agent), and a gathering of polyamines that have different physiological and cell parts.

A novel arrangement of β-amino amides consolidating melded heterocycles, i.e., triazolopiperazines, were orchestrated and assessed as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of diabetes type 2. Recently, the incretin hormone Glucagon like Peptide-1 (GLP-1) has been utilized to cure the type 2 diabetes. This peptide hormone is released from the gut in response to food intake. GLP-1 has a clearly well-known part in glucose homeostasis through the stimulus of insulin biosynthesis and excretion nd embarrassment of glucagon release. Prominently, GLP-1 normalizes the insulin in a rigorously glucose-dependent manner. Thus, GLP-1 therapy can pose either little risk or no risk of hypoglycemia. Another known impact of GLP-1 therapy comprises the decelerating gastric discharging and reduction of appetite. Active GLP-1 (GLP-1 [7-36] amide) is quickly ruined in vivo through the action of dipeptidyl peptidase IV (DPP-IV), a serine protease which splits a dipeptide from the N-terminus to give the inactive GLP-1 [9-36] amide. Therefore, a small-molecule inhibitor of (DPP-IV) would raise the half-life of active GLP-1 and extend the beneficial effects of this incretin hormone. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4] triazolo [4,3-a] pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl) butan-2-amine is a powerful, vocally active (DPP-IV) inhibitor  with excellent selectivity above the other proline-selective peptidases.

It likewise assumes a key part in excitation and power activities on neurons of spinal string. Glutamate satisfies the accompanying perspectives; (I) It has pre-synaptic area in particular neurons, (ii) Physiological boost discharges the glutamate to cause the post-synaptic activities, (iii) It decides the capacities continuing normally with transmitter, (iv) It likewise decides the activities that stop the transmitter's capacities.

β-Lactam or azetidin-2-one is a significant structural motif of the penicillin, cephalosporin, carbapenem, and carbacephem types of antibiotics. [37] Naturally arising as well as artificial monobactams, such as nocardicins and tabtoxin, are also recognized for their exclusive antibacterial activities. Cispentacin exhibits a strong antifungal in vitro activity against various Candida strains, e.g. Candida albicans, Candida krusei and Candida utilis. It revealed its weakness in vitro activity against Trichophyton mentagrophytes, while not in vitro activity was observed against Cryptococcus and Aspergillus species. [38-40] Sitagliptin phosphate (JanuviaTM) was the first permitted drug to switch the blood glucose concentration. [41] Sitagliptin comprises an (R)-3-amino-4-(2,4,5-trifluorophenyl) butanoic acid subunit. [42] Many further derivatives of sitagliptin have been synthesized and tested as potential antidiuretic drugs (Fig. 1). [43]

Fig. 1: Different antibiotics

Normal reactant for Nitric oxide (NO) and polyamine union through NO Synthase (NOS) is Arginine. It is changed over to ornithine by hydrolysis.[44] NO is major unwinding operator which is gotten from endothelium. [45] NO manages the blood stream in placenta and baby. [46] In this way, it transports the supplements and oxygen from mother to hatchling. [47] Arginine is likewise essential powerful hormone. [48] NO and polyamine are critical elements which direct the angiogenesis, embryogenesis, and development of hatchling and placenta. Consequently, Acidosis inside the muscles was portrayed as specific reason of unsettling influence in supplementation of β-alanine amid the substantial exercise. In this way, carnosine assumes a key part to control the pH of muscles. [49]

The blend of carnosine (Fig. 2) is completed in skeletal muscles. The amino corrosive L-histidine (Fig. 3) and β-alanine (Fig. 4) are used for amalgamation of carnosine inside skeletal muscles. β-alanine supplementation seemed to improve the substance of carnosine in muscles and furthermore the buffering limit of muscles. [50]

Profoundly thought and all around scattered β-amino corrosive in cerebrum cells is glutamate. It is investigated that glutamate has a noteworthy part in digestion inside the cerebrum.[51] The digestion of convoluted parts of glutamate inside the mind was accounted for by Waelsch and colleagues.[52]

These reports uncovered that glutamate is extremely noteworthy β-amino corrosive which has upgraded the psychological practices and furthermore vital in numerous mind issue, for example, epilepsy and mental hindrance. Numerous researchers additionally have seen that glutamate is imperative for cerebrum digestion. It detoxifies the exorbitant smelling salts inside the cerebrum.[53]

It is likewise fundamental β-amino corrosive amid the amalgamation of peptide, proteins and glutathione additionally. [54] It likewise goes about as antecedent for restraint of neurotransmitter Y-aminobutyric corrosive (GABA).

CONCLUSIONS- After a long exchange, it is understood that β-AAc and their subordinates are essential in lives of living beings. They are vital to their body organization. They are basic for their survival. They shield the living things against a large portion of sicknesses. They are likewise used to cure them. They assume a part in nourishing of creatures younger. In a matter of seconds, it can be said these are basic for living things. From this study, it has been concluded that β-amino acids and derivatives have potential therapeutic values on account of bearing varieties of biological activities including antifungal, antitubercular, antibacterial and anticancer. They are also used in the treatment of many diseases and health issues. β-amino acids gained significant interest due to their interesting pharmaceutical uses as hypoglycemic, anti-ketogenic characteristics, sterile and antifungal activities, anthelminthic as well as potent insecticidal characteristics. These are vital building blocks for the preparation of pharmaceutical and agrochemical target molecules. These are utilized in development of drugs, bimolecular structure and molecular recognition. It is expected that in future the more research studies on this will enhance the utilization and scope of β-AAc.

REFERENCES

1.      Ashfaq M, Tabassum R, Ahmad MM, Hassan NA, Oku H, Rivera G. Enantioselective synthesis of β-amino acids: A Review. Med. Chem, 2015; 5: 295-309.

2.      Cheng RP, Gellman SH, DeGrado WF. β-Peptides: from structure to function. Chemical reviews, 2001; 101(10): 3219-32.

3.      Juaristi E, Seebach D. Enantioselective Synthesis of α‐Substituted and α, β‐Disubstituted β‐Amino Acids via Chiral Derivatives of 3‐Aminopropionic Acid. ChemInform, 2010.

4.      Sibi MP, Manyem S. Enantioselective conjugate additions. Tetrahedron, 2000; 56(41): 8033-61.

5.      Beke T, Somlai C, Perczel A. Toward a rational design of β‐peptide structures. Journal of computational chemistry, 2006; 27(1): 20-38.

6.      Porter EA, Weisblum B, Gellman SH. Mimicry of host-defense peptides by unnatural oligomers: antimicrobial β-peptides. Journal of the American Chemical Society, 2002; 124(25): 7324-30.

7.      Wu G, Bazer FW, Davis TA, Jaeger LA, Johnson GA, Kim SW, Knabe DA, Meininger CJ, Spencer TE, Yin YL. Important roles for the arginine family of amino acids in swine nutrition and production. Livestock science, 2007; 112(1): 8-22.

8.      Artioli GG, Gualano B, Smith A, Stout J, Lancha Jr AH. Role of beta-alanine supplementation on muscle carnosine and exercise performance. Med Sci Sports Exerc, 2010; 42(6): 1162-73.

9.      Krebs HA. Metabolism of amino-acids: The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. Biochemical Journal, 1935; 29(8): 1951.

10.  Berl S, Lajtha A, Waelsch H. Amino acid and protein metabolism‐vi cerebral compartments of glutamic acid metabolism. Journal of Neurochemistry, 1961; 7(3): 186-97.

11.  Weil-Malherbe H. Significance of glutamic acid for the metabolism of nervous tissue. Physiological reviews, 1950; 30(4): 549-68.

12.  Meister A. Biochemistry of glutamate: glutamine and glutathione. Glutamic Acid: Advances in Biochemistry and Physiology, 1979: 69-84.

13.  Roberts E. and Frankel D. y-Aminobutyric acid in brain: its formation from  glutamic acid. J . Biol. Chem, 1950; 187: 55-63.

14.  Usherwood PN. Glutamate synapses and receptors on insect muscle. Advances in biochemical psychopharmacology, 1981; 27: 183-93.

15.  Sturman JA, Hayes KC. The biology of taurine in nutrition and development. InAdvances in nutritional research.Springer, Boston, MA, 1980; pp. 231-299.

16.  Sturman JA, Gargano AD, Messing JM, Imaki H. Feline maternal taurine deficiency: effect on mother and offspring. The Journal of nutrition, 1986; 116(4): 655-67.

17.  Sturman JA, Messing JM, Rossi SS, Hofmann AF, Neuringer MD. Tissue taurine content and conjugated bile acid composition of rhesus monkey infants fed a human infant soy-protein formula with or without taurine supplementation for 3 months. Neurochemical research, 1988; 13(4): 311-6.

18.  Sturman JA. Taurine in development. The Journal of nutrition, 1988; 118(10): 1169-76.

19.  Shinagawa S, Kanamaru T, Harada S, Asai M, Okazaki H. Chemistry and inhibitory activity of long chain fatty acid oxidation of emeriamine and its analogues. Journal of medicinal chemistry, 1987; 30(8): 1458-63.

20.  Kanamaru T, Shinagawa S, Asai M, Okazaki H, Sugiyama Y, Fujita T, Iwatsuka H, Yoneda M. Emeriamine, an antidiabetic β-aminobetaine derived from a novel fungal metabolite. Life sciences, 1985; 37(3): 217-23.

21.  Seebach D, Matthews JL. β-Peptides: a surprise at every turn. Chemical Communications, 1997; (21): 2015-22.

22.  Namikoshi M, Rinehart KL, Dahlem AM, Beasley VR, Carmichael WW. Total synthesis of Adda, the unique C20 amino acid of cyanobacterial hepatotoxins. Tetrahedron letters, 1989; 30(33): 4349-52. 

23.  Crews P, Manes LV, Boehler M. Jasplakinolide, a cyclodepsipeptide from the marine sponge, Jaspis sp. Tetrahedron letters, 1986; 27(25): 2797-800.

24.  Sibi MP, Manyem S, Salim M, Capretta A, Paulvannan K, Chen T, Hale R, Miyaoka H, Shigemoto T, Shinohara I, Suzuki A. 10. 1-Ethyl 2-Halopyridinium Salts, Highly Efficient Coupling Reagents for Hindered Peptide Synthesis both in Solution and the Solid-Phase. Tetrahedron, 2000; 56(41): 8033-206.

25.  Porter EA, Weisblum B, Gellman SH. Mimicry of host-defense peptides by unnatural oligomers: antimicrobial β-peptides. Journal of the American Chemical Society, 2002; 124(25): 7324-30.

26.  Beke T, Somlai C, Perczel A. Toward a rational design of β‐peptide structures. Journal of computational chemistry, 2006; 27(1): 20-38.

27.  Wu G, Bazer FW, Davis TA, Jaeger LA, Johnson GA, Kim SW, Knabe DA, Meininger CJ, Spencer TE, Yin YL. Important roles for the arginine family of amino acids in swine nutrition and production. Livestock science, 2007; 112(1): 8-22.

28.  Fazal-ur-Rehman M, Nagina NR. Biological Applications of β-amino acids and its derivatives, 2017.

29.  Zaki AM, Van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New England Journal of Medicine, 2012; 367(19): 1814-20.

30.  Gressner AM, Heinleu BK , Dooley S. et.al. J. Front. Biosci., 2002; 7: 793-807.

31.  Deaue R, Yau SD, Submamaryan RK, Larue B et.al., J. Nat. Med., 2003; 7: 907-913

32.  Olsson A, Csajbok L, Ost M, Höglund K, Nylen K, Rosengren L, Nellgard B, Blennow K. Marked increase of β-amyloid (1–42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury. Journal of neurology, 2004; 251(7): 870-6.

33.  Sugiarto H, Yu PL. Avian antimicrobial peptides: the defense role of β-defensins. Biochemical and biophysical research communications. 2004; 323(3): 721-7.

34.  Kim D, Wang L, Baconi M, Eiermann JG, et.al. (2R)-4-Oxo-4-[3-(Trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: A Potent, Orally Active Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes. J. Med. Chem., 2005; 48(1): 141-151.

35.  Hashimoto Y, Skacel M, Adams JC. Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker?. The international journal of biochemistry & cell biology, 2005; 37(9): 1787-804.

36.  Hayashi SI, Eguchi H, Tanimoto K, Yoshida T, Omoto Y, Inoue A, Yoshida N, Yamaguchi Y. The expression and function of estrogen receptor alpha and beta in human breast cancer and its clinical application. Endocrine-Related Cancer, 2003; 10(2): 193-202.

37.  Tseng ZH, Aouizerat BE, Pawlikowska L, Vittinghoff E, Lin F, Whiteman D, Poon A, Herrington D, Howard TD, Varosy PD, Hulley SB. Common ß-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease. Heart Rhythm, 2008; 5(6): 814-21.

38.  Kotanko P, Binder A, Tasker J, DeFreitas P, Kamdar S, Clark AJ, Skrabal F, Caulfield M. Essential hypertension in African Caribbeans associates with a variant of the β2-adrenoceptor. Hypertension, 1997; 30(4): 773-6.

39.  Brandt E, Petersen F, Ludwig A, Ehlert JE, Bock L, Flad HD. The β‐thromboglobulins and platelet factor 4: blood platelet‐derived CXC chemokines with divergent roles in early neutrophil regulation. Journal of leukocyte biology, 2000; 67(4): 471-8.

40.  Kohen R, Yamamoto Y, Cundy KC, Ames BN. Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proceedings of the National Academy of Sciences, 1988; 85(9): 3175-9.

41.  Dutka TL, Lamb GD. Effect of carnosine on excitation–contraction coupling in mechanically-skinned rat skeletal muscle. Journal of Muscle Research & Cell Motility, 2004; 25(3): 203-13.

42.  Dutka TL, Lamboley CR, McKenna MJ, Murphy RM, Lamb GD. Effects of carnosine on contractile apparatus Ca2+ sensitivity and sarcoplasmic reticulum Ca2+ release in human skeletal muscle fibers. Journal of applied physiology, 2011; 112(5): 728-36.

43.  Ririe DG, Roberts PR, Shouse MN, Zaloga GP. Vasodilatory actions of the dietary peptide carnosine. Nutrition, 2000; 16(3): 168-72.

44.  Baguet A, Reyngoudt H, Pottier A, Everaert I, Callens S, Achten E, Derave W. Carnosine loading and washout in human skeletal muscles. Journal of applied physiology, 2009; 106(3): 837-42.

45.  Derave W, Ozdemir MS, Harris RC, Pottier A, Reyngoudt H, Koppo K, Wise JA, Achten E. β-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. Journal of applied physiology, 2007; 103(5): 1736-43.

46.  Abe H. Role of histidine-related compounds as intracellular proton buffering constituents in vertebrate muscle. Biochemistry (Mosc).,  2000; 65(7): 757-65.

47.  Suzuki Y, Ito O, Mukai N, Takahashi H, Takamatsu K. High level of skeletal muscle carnosine contributes to the latter half of exercise performance during 30-s maximal cycle ergometer sprinting. The Japanese journal of physiology, 2002; 52(2): 199-205.

48.  Suzuki Y, Ito O, Takahashi H, Takamatsu K. The effect of sprint training on skeletal muscle carnosine in humans. International Journal of Sport and Health Science, 2004; 2: 105-10.

49.  Baguet A, Bourgois J, Vanhee L, Achten E, Derave W. Important role of muscle carnosine in rowing performance. Journal of Applied Physiology, 2010; 109(4): 1096-101.

50.  Harris RC, Tallon MJ, Dunnett M, Boobis L, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, Wise JA. The absorption of orally supplied β-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino acids, 2006; 30(3): 279-89.

51.  Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, Wise JA. Influence of β-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino acids, 2007; 32(2): 225-33.

52.  Boldyrev AA. Carnosine and oxidative stress in cells and tissues. Nova Publishers; 2007.

53.  Abernathy RL, Teal PE, Meredith JA, Nachman RJ. Induction of pheromone production in a moth by topical application of a pseudopeptide mimic of a pheromonotropic neuropeptide. Proceedings of the National Academy of Sciences, 1996; 93(22): 12621-5.

54.  Altstein M. Role of neuropeptides in sex pheromone production in moths. Peptides, 2004; 25(9): 1491-501.