Editing Penicillin (section)

== Structure ==
[[File:Penicillin-G 3D.png|thumb|right|Chemical structure of Penicillin G. The sulfur and nitrogen of the five-membered [[thiazolidine]] ring are shown in yellow and blue respectively. The image shows that the thiazolidine ring and fused four-membered ''β''-lactam are not in the same [[Plane (geometry)|plane]].]]

The term "[[penam]]" is used to describe the common core skeleton of a member of the penicillins. This core has the molecular formula R-C<sub>9</sub>H<sub>11</sub>N<sub>2</sub>O<sub>4</sub>S, where R is the variable side chain that differentiates the penicillins from one another. The penam core has a [[molar mass]] of 243 g/mol, with larger penicillins having molar mass near 450—for example, cloxacillin has a molar mass of 436 g/mol. 6-APA (C<sub>8</sub>H<sub>12</sub>N<sub>2</sub>O<sub>3</sub>S) forms the basic structure of penicillins. It is made up of an enclosed dipeptide formed by the condensation of {{nowrap|<small>L</small>-cysteine}} and {{nowrap|<small>D</small>-valine}}. This results in the formations of β-lactam and thiazolidinic rings.<ref name=":6">{{Cite journal| vauthors = Fernandes R, Amador P, Prudêncio C |date=2013|title=β-Lactams: chemical structure, mode of action and mechanisms of resistance|journal=Reviews in Medical Microbiology|language=en|volume=24|issue=1|pages=7–17|doi=10.1097/MRM.0b013e3283587727|hdl=10400.22/7041|doi-access=free|hdl-access=free}}</ref>

The key structural feature of the penicillins is the four-membered β-lactam ring; this structural [[moiety (chemistry)|moiety]] is essential for penicillin's antibacterial activity. The β-lactam ring is itself fused to a five-membered [[thiazolidine]] ring. The fusion of these two rings causes the β-lactam ring to be more reactive than monocyclic β-lactams because the two fused rings distort the β-lactam [[amide bond]] and therefore remove the [[Resonance (chemistry)|resonance stabilisation]] normally found in these chemical bonds.<ref>Nicolaou (1996), p. 43.</ref> An acyl side side chain attached to the β-lactam ring.<ref>{{cite journal | vauthors = Fisher JF, Mobashery S | title = Three decades of the class A beta-lactamase acyl-enzyme | journal = Current Protein & Peptide Science | volume = 10 | issue = 5 | pages = 401–07 | date = October 2009 | pmid = 19538154 | pmc = 6902449 | doi = 10.2174/138920309789351967 }}</ref>

A variety of β-lactam antibiotics have been produced following chemical modification from the 6-APA structure during synthesis, specifically by making chemical substitutions in the acyl side chain. For example, the first chemically altered penicillin, methicillin, had substitutions by methoxy groups at positions 2’ and 6’ of the 6-APA benzene ring from penicillin G.<ref name=":6" /> This difference makes methicillin resistant to the activity of [[Beta-lactamase|β-lactamase]], an enzyme by which many bacteria are naturally unsusceptible to penicillins.<ref name=":9">{{cite journal | vauthors = Morell EA, Balkin DM | title = Methicillin-resistant Staphylococcus aureus: a pervasive pathogen highlights the need for new antimicrobial development | journal = The Yale Journal of Biology and Medicine | volume = 83 | issue = 4 | pages = 223–33 | date = December 2010 | pmid = 21165342 | pmc = 3002151 }}</ref>