関: gramicidin

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the 19th letter of the Roman alphabet (同)s
an antibiotic produced by a soil bacterium; used chiefly as an antiseptic in treating local infections produced by Gram-positive bacteria

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sulfurの化学記号 / {略}South[ern]

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/16 15:34:33」(JST)

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Gramicidin S or Gramicidin Soviet^[1] is an antibiotic effective against some Gram positive and Gram negative bacteria as well as some fungi. It is a derivative of gramicidin, produced by the Gram positive bacterium Bacillus brevis. Gramicidin S is a cyclodecapeptide, constructed as two identical pentapeptides joined head to tail, formally written as cyclo(-Val-Orn-Leu-D-Phe-Pro-)₂. That is to say, it forms a ring structure composed of five different amino acids, each one used twice within the structure.^[2] Another interesting point is that it utilizes two amino acids uncommon in peptides: ornithine as well as the atypical stereoisomer of phenylalanine. It is synthesized by gramicidin S synthetase.^[3]

History

Gramicidin S was discovered by Russian microbiologist Georgyi Frantsevitch Gause and his wife Maria Brazhnikova in 1942. Within the year Gramicidin S was being used in Soviet military hospitals to treat infection and eventually found usage at the front lines of combat by 1946.^[4] Gause was awarded the Stalin Prize for Medicine for his discovery in 1946. In 1944, Gramicidin S was sent by the Ministry of Health of the USSR to Great Britain via the International Red Cross in a collaborative effort to establish the exact structure. English chemist Richard Synge proved that the compound was an original antibiotic and a polypeptide using paper chromatography.^[5] He would later go on to receive the Nobel Prize for his work in chromatography. The crystal structure was finally established by Dorothy Hodgkin and Gerchardt Schmidt. The importance of Gramicidin S and antibiotic research in general was so great that Gause was not persecuted during the period of Lysenkoism in the USSR, while many of his colleagues were being executed. Indeed, it was his need for developing new strains to mass produce antibiotics that allowed politically sanctioned collaborations with geneticists like Joseph Rapoport and Alexander Malinovsky, who would both actively participate in the downfall of Lysenkoism.^[4]

Structure and Pharmacological effect

Crystal structure of modified Gramicidin S. Modification includes Boc groups on the ornithine as well as methylation of select amide nitrogens to force cyclic conformation.^[6]

Structurally, Gramicidin S differs from Gramicidin D, which is a linear peptide and forms a beta helix in cellular membranes. The mode of action is not entirely agreed upon, but it is generally accepted that it is the disruption of the barrier properties of cellular membranes which causes cell death. Recent research reveals that Gramicidin S interacts more so with anionic membranes (such as those of bacteria) vs. zwitterionic membranes and more fluid membranes.^[7] It has a molecular mass of ca. 1,140 and is a solid, usually encapsulated in two-percent sterile spirit solution. In vitro assays show it has a MIC of 5-15 μg/mL.^[8]

Use

Gramicidin S has historically been employed as a topical antibiotic for the treatment of infections from superficial wounds. It exhibits strong antibiotic activity against a broad spectrum of Gram negative and Gram-positive bacteria and against several pathogenic fungi. Like Gramicidin D, Gramicidin S causes hemolysis at low concentrations, thus is not an effective drug for the treatment of systemic infections. Additionally, Gramicidin S has been employed as a spermicide and therapeutic for genital ulcers caused by sexually transmitted disease.^[9]

References

^ Gause, G. F.; Brazhnikova, M. G. (1944), "Gramicidin S and its use in the Treatment of Infected Wounds", Nature 154 (3918): 703–703, doi:10.1038/154703a0.
^ Llamas-Saiz, Antonio; Grotenbreg, GM; Overhand, M; Van Raaij, MJ (2007), "Double-stranded helical twisted b-sheet channels in crystals of gramicidin S grown in the presence of trifluoroacetic and hydrochloric acids", Acta Crystallographica Section D D63 (Pt 3): 401–407, doi:10.1107/S0907444906056435, PMID 17327677
^ Brick, Peter; Stachelhaus, T; Marahiel, MA; Brick, P (1997), "Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S", The EMBO Journal 16 (14): 4174–4183, doi:10.1093/emboj/16.14.4174, PMC 1170043, PMID 9250661
^ ^a ^b Gall, YM; Konashev, MB (2001), "The discovery of Gramicidin S: the Intellectual Transformation of G.F. Gause from Biologist to Researcher of Antibiotics and on its Meaning for the Fate of Russian Genetics", Hist. Phil. Life Sci. 23 (1): 137–50, PMID 12212443
^ R.L.M. Synge - Britannica Online Encyclopedia
^ Yamada, Keiichi; Unno, Masafumi; Kobayashi, Kyoko; Oku, Hiroyuki; Yamamura, Hatsuo; Araki, Shuki; Matsumoto, Hideyuki; Katakai, Ryoichi et al. (2002), "Stereochemistry of Protected Ornithine Side Chains of Gramicidin S Derivatives: X-ray Crystal Structure of the Bis-Boc-tetra-N-methyl Derivative of Gramicidin S", Journal of the American Chemical Society 124 (43): 12684–12688, doi:10.1021/ja020307t, PMID 12392415
^ Prenner, E. J.; Kiricsi, M; Jelokhani-Niaraki, M; Lewis, RN; Hodges, RS; McElhaney, RN (2004), "Structure-Activity Relationships of Diastereomeric Lysine Ring Size Analogs of the Antimicrobial Peptide Gramicidin S: MECHANISM OF ACTION AND DISCRIMINATION BETWEEN BACTERIAL AND ANIMAL CELL MEMBRANES", Journal of Biological Chemistry 280 (3): 2002–2011, doi:10.1074/jbc.M406509200, PMID 15542606.
^ Xiao, Jingbo; Weisblum, Bernard; Wipf, Peter (2005), "Electrostatic versus Steric Effects in Peptidomimicry: Synthesis and Secondary Structure Analysis of Gramicidin S Analogues with (E)-Alkene Peptide Isosteres", Journal of the American Chemical Society 127 (16): 5742–5743, doi:10.1021/ja051002s, PMID 15839644.
^ Krylov YuF (1993) Compendium of medicinal products of Russia. Inpharmchem Press, Moscow, p 343 [in Russian]

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English Journal

When and how the melittin ion channel exhibits ohmic behavior.

Becucci L1, Aloisi G2, Guidelli R3.
Bioelectrochemistry (Amsterdam, Netherlands).Bioelectrochemistry.2017 Feb;113:51-59. doi: 10.1016/j.bioelechem.2016.10.001. Epub 2016 Oct 6.
Melittin exhibits an ohmic behavior in a lipid bilayer having a DOPC distal leaflet and interposed between a 2.25nm tetraethyleneoxy chain tethered to a mercury drop and an aqueous solution. This behavior is induced in a pH6.8 buffer solution of 0.8μg/mL melittin by a pretreatment consisting of ser
PMID 27732908

Local Anesthetics Affect Gramicidin A Channels via Membrane Electrostatic Potentials.

Efimova SS1, Zakharova AA2, Schagina LV2, Ostroumova OS2.
The Journal of membrane biology.J Membr Biol.2016 Dec;249(6):781-787. Epub 2016 Sep 3.
The effects of local anesthetics (LAs), including aminoamides and aminoesters, on the characteristics of single gramicidin A (GA) channels in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers were studied. Aminoamides, namely lidocaine (LDC), prilocaine (PLC), mepivacaine (MPV), and bupivacai
PMID 27592116

Directional Potassium Transport through a Unimolecular Peptide Channel.

Su G1, Zhang M1, Si W1, Li ZT1, Hou JL1.
Angewandte Chemie (International ed. in English).Angew Chem Int Ed Engl.2016 Nov 14;55(47):14678-14682. doi: 10.1002/anie.201608428. Epub 2016 Oct 18.
Three unimolecular peptide channels have been designed and prepared by using the β-helical conformation of gramicidin A (gA). The new peptides bear one to three NH3+ groups at the N-end and one to three CO2- groups at the C-end. These zwitterionic peptides were inserted into lipid bilayers in an
PMID 27754610

Japanese Journal

High extracellular Ca2+ stimulates Ca2+-activated Cl- currents in frog parathyroid cells through the mediation of arachidonic acid cascade.

Okada Yukio,Imendra Kotapola G,Miyazaki Toshihiro,Hotokezaka Hitoshi,Fujiyama Rie,Toda Kazuo
PLoS One 6(4), e19158, 2011-04-29
… Gramicidin-perforated whole-cell recording displayed the shift of the reversal potential in extracellular Ca(2+)-induced current, suggesting the change of intracellular Cl(-) concentration in a few minutes. …
NAID 120003238497

28aGV-3 イオンチャネルgramicidin Aに対するオーダーN法大規模第一原理計算(28aGV 生物物理,領域12(ソフトマター物理,化学物理,生物物理))

有田通朗,宮崎剛,Todorovic M.,篠田渉,Bowler D. R.
日本物理学会講演概要集 66(1-2), 416, 2011-03-03
NAID 110008611227

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★リンクテーブル★

リンク元	「グラミシジンS」
拡張検索	「gramicidin S hydrochloride」
関連記事	「S」

「グラミシジンS」

Gramicidin S
Systematic (IUPAC) name
	Gramicidin S
Clinical data
Pregnancy cat.	?
Legal status	?
Routes	Topical
Identifiers
CAS number	113-73-5
ATC code	?
PubChem	CID 73357
ChemSpider	66085
ChEBI	CHEBI:5530
ChEMBL	CHEMBL373496
NIAID ChemDB	002002
Chemical data
Formula	C60H92N12O10
Mol. mass	1140.7059 g/mol
	SMILES CC(C)C[C@H]1C(=O)N[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N3CCC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)CCCN)C(C)C)Cc4ccccc4)CC(C)C)CCCN)C(C)C)Cc5ccccc5;
	InChI InChI=1S/C60H92N12O10/c1-35(2)31-43-53(75)67-45(33-39-19-11-9-12-20-39)59(81)71-29-17-25-47(71)55(77)70-50(38(7)8)58(80)64-42(24-16-28-62)52(74)66-44(32-36(3)4)54(76)68-46(34-40-21-13-10-14-22-40)60(82)72-30-18-26-48(72)56(78)69-49(37(5)6)57(79)63-41(23-15-27-61)51(73)65-43/h9-14,19-22,35-38,41-50H,15-18,23-34,61-62H2,1-8H3,(H,63,79)(H,64,80)(H,65,73)(H,66,74)(H,67,75)(H,68,76)(H,69,78)(H,70,77)/t41-,42-,43-,44-,45+,46+,47-,48-,49-,50-/m0/s1 ; Key:IUAYMJGZBVDSGL-XNNAEKOYSA-N ;
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