peptide chain

Antimicrobial Agents - Inhibition of DNA and Protein Synthesis

Bacterial chromosome replication

DNA replication

Bacterial Topoisomerases 

  • maintain DNA in appropriate state of supercoiling 
  • cut and reseal DNA
  • DNA gyrase (topoisomerase II) introduces negative supercoils 
  • Topoisomerase IV decatenates circular chromosomes 
  • these are the targets of the quinolone antibacterial agents 

Quinolones

  • bind to bacterial DNA gyrase and topoisomerase IV after DNA strand breakage 
  • prevent resealing of DNA 
  • disrupt DNA replication and repair 
  • bactericidal (kill bacteria)

Fluoroquinolone is particularly useful against

  • Gram +ves: Staphylococcus aureus, streptococci 
  • Gram -ves: Enterobacteriacea; Pseudomonas aeruginosa 
  • Anaerobes: e.g. Bacteroides fragilis 
  • many applications e.g. UTIs, prostatitis, gastroenteritis, STIs 

Adverse effects

  • Relatively well tolerated
  • GI upset in ~ 5% of patients 
  • allergic reactions (rash, photosensitivity) in 1 - 2% of patients 

Inhibition of Bacterial Protein Synthesis 

Macrolides 

  • in 1952: Erythromycin was isolated as the first macrolide (Streptomyces erythreus) 
  • Newer macrolides: clarithromycin, azithromycin 
  • Structurally they consist of a lactone ring (14- to 16-membered) + two attached deoxy sugars 

Mode of action 

  • bind reversibly to bacterial 50S ribosomal subunit 
  • causes growing peptide chain to dissociate from ribosome → inhibiting protein synthesis 
  • bacteriostatic (stops reproduction)

Macrolides’ spectrum of activity

  • good antistaphylococcal and antistreptococcal activity 
  • treatment of respiratory & soft tissue infections and sensitive intracellular pathogens • e.g. Chlamydia, Legionella 

Adverse effects

  • Generally well tolerated
  • nausea 
  • vomiting 
  • diarrhoea 
  • rash 

Aminoglycosides

  • large family of antibiotics produced by various species of Streptomyces (“mycin”) and Micromonospora (“micin”) 
  • include: streptomycin, neomycin, kanamycin, gentamicins, tobramycin 
  • Structure = linked ring system composed of aminosugars and an aminosubstituted cyclic polyalcohol 

Mode of action of aminoglycosides

  • Bind irreversibly to 30S ribosomal subunit 
  • disrupt elongation of nascent peptide chain 
  • translational inaccuracy → defective proteins 
  • bactericidal 

Spectrum of activity 

  • broad spectrum; mainly aerobic G-ve bacilli (e.g. P. aeruginosa) 
  • used to treat serious nosocomial infections (hospital acquired infections)
  • First TB antibiotic
  • Used for cystic fibrosis 

Adverse effects

  • all aminoglycosides have low Therapeutic Index (only a small amount needed to become toxic)
  • renal damage, ototoxicity, loss of balance, nausea 

anonymous asked:

i want to do a neurotransmitters tattoos. i thought of oxytocin on my right forearm (and thats the start) but i want to have like 4-6 neurotransmitters around my body with structure and function (the oxytocin one will also have the peptide chain name) and now idk what the other 3-5 will be. can you help in that area?

uhhh dopamine and serotonin come to mind but i’m not a neurobiologists so 

Bradykinin is a peptide that causes blood vessels to dilate (enlarge), and therefore causes blood pressure to fall. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin (by inhibiting its degradation) further lowering blood pressure. Bradykinin dilates blood vessels via the release of prostacyclin, nitric oxide, and Endothelium-Derived Hyperpolarizing Factor.

Image: The structure of Bradykinin. Bradykinin is a 9-amino acid peptide chain. The amino acid sequence of bradykinin is Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg. Its empirical formula is therefore C50H73N15O11.

Bacterial Taxonomy 1 - Classification Based on Morphology and the Gram Stain. 

Taxonomy, is literally the science of classification. Look at the picture above, and imagine that all those little divisions, like “firmicutes” are different phyla under the kingdom of bacteria. Then those phyla are further subdivided into different classes, then orders, then families, then genera, and then finally species! Take a look at how this works for one particular bacteria, called streptococcus mutans. 

Wow, there’s a lot to classify, probably why it’s taxonomy: it’s such a taxing job.

Ahem, right, so. As you’ve probably noticed, Streptococcus mutans is named using its Genera and its Species name. Similarly, all organisms have a scientific name comprising of two parts: The genus, followed by the species. It is very important to classify organisms in this way because: 

  1. It establishes criteria for identifying organisms. 
  2. Allows arrangement of related organisms into groups. 
  3. Provides important information on how organisms evolved.  

Bacteria are classified, usually, according to their morphological, metabolic and biochemical differences, although genetic and immunologic factors are also now being considered. 

One of the earliest, and most fundamental methods of classifying bacteria depended on the use of the Gram Stain. 

Gram Stain

Unlike large organisms like humans, parrots and dra-, erm, Komodo Dragons, which are easy to spot and have a distinct appearance to the eye, bacteria are colourless and invisible to light microscopy. Thus, gram staining had to be developed to give bacteria a colour, and visualize them. Since bacteria would either respond to the stain, or not, all bacteria were subsequently classified into gram-positive and gram-negative bacteria. 

There are 4 steps to the Gram Stain Procedure. 

  1. Pour crystal violet stain (a blue dye) and wait for 60 seconds. 
  2. Wash off with water and flood with iodine solution. Wait for 60 seconds. 
  3. Wash off with water and then “decolourize” with 95% alcohol solution. 
  4. Counter-stain with safranin (a red dye). Wait 30 seconds and then wash off with water. 

Basically, when viewed under the microscope, cells that absorb the crystal violet dye and hold on to it become blue: These are gram-positive. Alternatively, if the crystal violet is washed off by the 95% alcohol, the cells absorb the safranin and appear red. These are gram-negative. 

Gram Positive = Blue 

Imagine yourself sitting by the beach, opposite crystal blue waters, or kayaking across deep waters, or even river tubing across the bluest of rivers.. won’t you say yes to that? So, Blue = Positive. Note that Gram-Positive bacteria may also appear purple if the red safranin is not effectively washed off. This is because blue + red is purple. 

Gram Negative = Red

Now you’re sitting in sweltering red heat, sweat pouring down your body, the sun red in the sky. You don’t want that, do you? Or for comic book fans, you can picture Superman’s face when he sees a Red Sun in the sky. NOPE, thinks Superman. So Red = Negative. 

This difference occurs due to a difference in morphology of the bacteria. 

Gram Positive vs Gram Negative Bacteria 

Unlike eukaryotic animal cells which contain only one cell membrane composed of phospholipid separating the nucleus from the ECF, both gram-positive and gram negative bacteria contain more than 1 layer: the layer outside the bacterial cytoplasmic membrane is the peptidoglycan layer. 

Keep reading

Antimicrobial Agents  - Cell wall inhibitors

Based on mode of action • divided into families based on chemical structure

 Modes of action Interference with: 

  • cell wall synthesis 
  • protein synthesis 
  • nucleic acid synthesis 
  • plasma membrane integrity 
  • metabolic pathway 

Inhibitors of Bacterial Cell Wall (peptidoglycan) Synthesis 

  • The Beta-lactam Family 
  • The Glycopeptides 


Peptidoglycan is composed of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) repeat units, and amino acids.  Each NAM is linked to peptide chain and the peptide chains are cross-linked.

β-lactams 

  • Includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems.
  • class of broad-spectrum antibiotics containing a β-lactam ring
  • Bacterial transpeptidase enzymes are responsible for catalysing cross-linking of the peptide chains
  • β-lactam ring bind to these transpeptidases – this inhibits cross-linking between peptide chains and prevents synthesis of stable PG
  • Cell wall synthesis ceases and the bacterial cells eventually die due to osmotic instability or autolysis. 

Glycopeptides 

Polypeptide agents - basic structural elements amino acids 

Vancomycin

  • complexes with peptide portion of peptidoglycan’s precursor units 
  • vancomycin is a large hydrophilic molecule able to form hydrogen bonds with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides
  • preventing PG transglycosylation reaction – PG precursor subunits (NAG-NAM+peptide) cannot be inserted into peptidoglycan matrix;
  • Vancomycin also alters bacterial-cell-membrane permeability and RNA synthesis

Uses:  serious Gram positive infections e.g. MRSA wound infection

Adverse effects:

  • damage to auditory nerve 
  • hearing loss (ototoxicity) 
  • “Red man/neck” syndrome - rash on face, neck, upper torso