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DSIP is a short, unmodified linear nonapeptide with no such protection

[2] Use of estradiol cypionate injection is contraindicated in individuals with undiagnosed abnormal vaginal bleeding, known or suspected breast cancer or other estrogen-dependent neoplasia, active or prior venous thromboembolism, recent arterial thrombo-occlusive disease such as stroke or myocardial infarction, severe hepatic impairment, a history of hypersensitivity to estradiol or any excipients, and in those who are or may become pregnant

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This is most likely attributed to the inability of the constrained 13- and 14-membered macrocycles to adopt the proper transition states required for cleavage of the N-terminal peptide bond (Andersson et al., 2011) (Figure 8)