Gramicidin B

Gramicidin B
Clinical data
Other names	formyl-L-Val-Gly-L-Ala-D-Leu-L-Ala-D-Val-L-Val-D-Val-L-Trp-D-Leu-L-Phe-D-Leu-L-Trp-D-Leu-L-Trp-ethanolamine
Routes of; administration	topical
Identifiers
	IUPAC name Gramicidin B;
CAS Number	9062-60-6 ;
PubChem CID	25244501;
ChemSpider	26333279 ;
UNII	7F82B1QV4X;
ChEBI	CHEBI:188873;
Chemical and physical data
Formula	C97H139N19O17
Molar mass	1843.295 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](Cc1c[nH]c2c1cccc2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](Cc4c[nH]c5c4cccc5)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](Cc6c[nH]c7c6cccc7)C(=O)NCCO)NC(=O)CNC(=O)[C@H](C(C)C)NC=O;
	InChI InChI=1S/C97H139N19O17/c1-51(2)38-71(106-84(120)59(17)104-79(119)49-102-94(130)80(55(9)10)103-50-118)87(123)105-60(18)85(121)114-82(57(13)14)96(132)116-83(58(15)16)97(133)115-81(56(11)12)95(131)113-78(45-64-48-101-70-35-27-24-32-67(64)70)93(129)109-72(39-52(3)4)88(124)110-75(42-61-28-20-19-21-29-61)91(127)107-74(41-54(7)8)90(126)112-77(44-63-47-100-69-34-26-23-31-66(63)69)92(128)108-73(40-53(5)6)89(125)111-76(86(122)98-36-37-117)43-62-46-99-68-33-25-22-30-65(62)68/h19-35,46-48,50-60,71-78,80-83,99-101,117H,36-45,49H2,1-18H3,(H,98,122)(H,102,130)(H,103,118)(H,104,119)(H,105,123)(H,106,120)(H,107,127)(H,108,128)(H,109,129)(H,110,124)(H,111,125)(H,112,126)(H,113,131)(H,114,121)(H,115,133)(H,116,132)/t59-,60-,71+,72+,73+,74+,75-,76-,77-,78-,80-,81+,82+,83-/m0/s1 ; Key:LQSMEVHEYXACJP-DSHASFMGSA-N ;
	(what is this?) (verify)

Gramicidin B is part of the collective Gramicidin D that is an antibiotic obtained from a soil microbe- Bacillus brevis. This antibiotic forms channels in the cell membrane through which cations inside the cell begin to leave, thus disrupting the ion potential and eventually killing the cell. Gramicidin B makes up 6% of Gramicidin D while Gramicidin A and C make up 80% and 14% respectively.^[1] Gramicidin D is a linear pentadecapeptide made up of 15 amino acids. The 11th amino acid in these chains leads to the three different types of gramicidins. Gramicindin A contains tryptophan in the 11th position while B and C have phenylalanine and tyrosine respectively.^[1]

Biosynthesis

Gramicidin B is composed of 15 amino acids that alternate between the L and D configuration. It is a linear peptide that is formed by four nonribosomal peptide synthetases (NRPSs), LgrABCD.^[2]

The N terminus is protected by a formyl group while the C terminus is protected by an ethanolamine. This is done so that the peptide will not have ‘open ends’ that are subjected to degradation by proteases. It has also been noted that the amino acids that are in Gramicidin B are solely hydrophobic amino acids. This is causes the peptide to be insoluble in water and unable to form zwitterions. Due to the alternating configuration of the amino acids, a beta helix with all the side chains pointing outward is formed.^[3]

References

^ ^a ^b Weinstein S, Wallace BA, Morrow JS, Veatch WR (October 1980). "Conformation of the gramicidin A transmembrane channel: A 13C nuclear magnetic resonance study of 13C-enriched gramicidin in phosphatidylcholine vesicles". Journal of Molecular Biology. 143 (1): 1–19. doi:10.1016/0022-2836(80)90121-7. PMID 6160255.
^ Schracke N, Linne U, Mahlert C, Marahiel MA (June 2005). "Synthesis of linear gramicidin requires the cooperation of two independent reductases". Biochemistry. 44 (23): 8507–13. doi:10.1021/bi050074t. PMID 15938641.
^ Kessler N, Schuhmann H, Morneweg S, Linne U, Marahiel MA (February 2004). "The linear pentadecapeptide gramicidin is assembled by four multimodular nonribosomal peptide synthetases that comprise 16 modules with 56 catalytic domains". The Journal of Biological Chemistry. 279 (9): 7413–9. doi:10.1074/jbc.M309658200. PMID 14670971.

[Weinstein-1] Weinstein S, Wallace BA, Morrow JS, Veatch WR (October 1980). "Conformation of the gramicidin A transmembrane channel: A 13C nuclear magnetic resonance study of 13C-enriched gramicidin in phosphatidylcholine vesicles". Journal of Molecular Biology. 143 (1): 1–19. doi:10.1016/0022-2836(80)90121-7. PMID 6160255.

[Schracke-2] Schracke N, Linne U, Mahlert C, Marahiel MA (June 2005). "Synthesis of linear gramicidin requires the cooperation of two independent reductases". Biochemistry. 44 (23): 8507–13. doi:10.1021/bi050074t. PMID 15938641.

[Kessler-3] Kessler N, Schuhmann H, Morneweg S, Linne U, Marahiel MA (February 2004). "The linear pentadecapeptide gramicidin is assembled by four multimodular nonribosomal peptide synthetases that comprise 16 modules with 56 catalytic domains". The Journal of Biological Chemistry. 279 (9): 7413–9. doi:10.1074/jbc.M309658200. PMID 14670971.

[1]

[2]

[3]