Semi-synthetic heparin derivatives: chemical modifications of heparin beyond chain length, sulfate substitution pattern and N-sulfo/N-acetyl groups

Introductory Chapter: Multi-Aspect Bibliographic Analysis of the Synergy of Technical, Biological and Medical Sciences Concerning Materials and Technologies Used for Medical and Dental Implantable Devices

“…This also applies tyrosinase, phosphopantetheinyl transferase, lysyl oxidase, plasma amine oxidase, and phosphatases [498]. It made it possible in particular to develop new gels by engrafting tyramine groups into natural and synthetic polymers such as dextran, hyaluronic acid, alginate, cellulose, gelatin, heparin and PEG-PPO [499][500][501][502][503][504][505]509].…”

Old and new applications of non-anticoagulant heparin

“…Early chemical modifications included selective O-acylation in 1947 and N-desulfation in 1958 [87]. N-desulfated heparin, named "heparamine", showed reduced anticoagulant activity, experimental beneficial effects in preventing hepatic and renal damage by ischemia and reperfusion, as well as in inhibiting angiogenesis and experimental metastatic gastric cancer [88].…”

“…An oversulfated LMWH preparation was found beneficial in an iron restricted anaemia model through inhibition of the peptide hormone Hepcidin [68]. Various types of derivatives, chemical processes, some biological interactions and activities are reported in dedicated reviews [87,89,92,93]. While the early structurally defined heparin binding to AT and thrombin supported the search of new anticoagulants and antithrombotics, only a few of the heparin interactions with the multitude of proteins involved, for example in inflammation [5], angiogenesis, metastasis and cancer [94] as well as atherosclerosis (LDL) [95] have been fully investigated to date.…”

Heparin-Like Drugs with Antiangiogenic Activity

“…Additional local flexibility was obtained by glycol-splitting that act as flexible joints along the heparin chain were conformation changes can be induced by the protein interaction. Chemical modifications of heparin have been reviewed in depth by Casu et al (Casu et al, 2002b) and Fernandez et al (Fernández et al, 2006) that described the biological effect of Nsulfate removal, N-acylation of native amino groups or amino groups created after Ndesulfation, O-sulfate removal, sulfation of hydroxyl groups (existing in the molecule or exposed by desulfation), acylation of unsubstituted hydroxyl groups and glycol-splitting. Several groups have dedicated their research activity of the last decades to understand the structure-activity relationship of this molecule by its controlled chemical modification.…”