The exact mechanism of DNA strand scission is unresolved, but it has been suggested that bleomycin chelates metal ions (primarily iron), producing a pseudoenzyme that reacts with oxygen to produce superoxide and hydroxide free radicals that cleave DNA. An alternative hypothesis states that bleomycin may bind at specific sites in the DNA strand and induce scission by abstracting the hydrogen atom from the base, resulting in strand cleavage as the base undergoes a Criegee-type rearrangement, or forms an alkali-labile lesion. In addition, these complexes also mediate lipid peroxidation and oxidation of other cellular molecules. Therefore, bleomycin is used in combination with doxorubicin in Hodgkins lymphoma, as they have additive and complementary effects on the DNA, since doxorubicin acts by intercalating between DNA  strands, and also acts on topoisomerase II enzyme thus relaxing the topoisomerase complexes. Biosynthesis
Bleomycin is a nonribosomal peptide that is a hybrid peptide-polyketide natural product. The peptide/polyketide/peptide backbone of the bleomycin aglycon is assembled by the bleomycin megasynthetase, which is made of both nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules. Nonribosomal peptides and polyketides are synthesized from amino acids and short carboxylic acids by NRPSs and PKSs, respectively. These NRPSs and PKSs use similar strategies for the assembly of these two distinct classes of natural products. Both NRPs and type I PKSs are organized into modules. The structural variations of the resulting peptide and polyketide products are determined by the number and order of modules on each NRPS and PKS protein.
Plasminogen, sold under the brand name Ryplazim, is a biologic medication for the treatment of hypoplasminogenemia (plasminogen deficiency type 1). It is purified from human plasma and is administered intravenously.The most common side effects include abdominal pain, bloating, nausea, bleeding, limb pain, fatigue, constipation, dry mouth, headache, dizziness, joint pain, and back pain.Individuals with hypoplasminogenemia lack a protein called plasminogen, which is responsible for the ability of the body to break down fibrin clots. Plasminogen deficiency leads to an accumulation of fibrin, causing the development of growths (lesions) that can impair normal tissue and organ function and may lead to blindness when these lesions affect the eyes.Plasminogen, human-tvmh was approved for medical use in the United States in June 2021. It is the first therapy for hypoplasminogenemia approved by the U.S. Food and Drug Administration (FDA). Medical uses
Plasminogen, human-tvmh is indicated for the treatment of people with plasminogen deficiency type 1, also referred to as hypoplasminogenemia, a disorder that can impair normal tissue and organ function and may lead to blindness. History
The effectiveness and safety of plasminogen is primarily based on one single-arm, open-label (unblinded) clinical trial enrolling 15 adult and pediatric participants with plasminogen deficiency type 1. All participants received plasminogen administered every two to four days for 48 weeks.